The vagus nerve and the nicotinic anti-inflammatory pathway
Nature Reviews Drug DiscoveryPublished 1 August 2005
Luis Ulloa
Citations462
SJR quartileQ1
SJR score30.51
SNIP23.21
Generate an AI Snapshot to get a quick, structured summary of this paper.
Study Snapshot
ObjectiveStudy objective
MethodsResearch methodology
PopulationPopulation studied
Sample sizeSample sizes
OutcomesStudy outcomes here
ResultsStudy results comes here
LimitationsResearch study limitations comes here
A concise AI-generated summary of the paper will appear here once you click Generate AI Snapshot.
TL;DR
Recent advances supporting the therapeutic potential of selective nicotinic agonists in several diseases are reviewed, suggesting that selective agonists for α7nAChR could represent a promising pharmacological strategy against infectious and inflammatory diseases.
Abstract
Physiological anti-inflammatory mechanisms are selected by evolution to effectively control the immune system and can be exploited for the treatment of inflammatory disorders. Recent studies indicate that the vagus nerve (which is the longest of the cranial nerves and innervates most of the peripheral organs) can modulate the immune response and control inflammation through a 'nicotinic anti-inflammatory pathway' dependent on the alpha7-nicotinic acetylcholine receptor (alpha7nAChR). Nicotine has been used in clinical trials for the treatment of ulcerative colitis, but its clinical applications are limited by its unspecific effects and subsequent toxicity. This article reviews recent advances supporting the therapeutic potential of selective nicotinic agonists in several diseases. Similar to the development of alpha- and beta-agonists for adrenoceptors, selective agonists for alpha7nAChR could represent a promising pharmacological strategy against infectious and inflammatory diseases.
Keywords
NeuroscienceBiochemistry, Genetics and Molecular Biology
Critical Care MedicineEpidemiology of severe sepsis in the United States: Analysis of incidence, outcome, and associated costs of care
8,486 Citations2001Derek C. Angus, Walter T. Linde‐Zwirble +4 more
Severe sepsis is a common, expensive, and frequently fatal condition, with as many deaths annually as those from acute myocardial infarction, and is especially common in the elderly and is likely to increase substantially as the U.S. population ages.
New England Journal of MedicineThe Epidemiology of Sepsis in the United States from 1979 through 2000
5,794 Citations2003Greg S. Martin, David M. Mannino +2 more
The rate of sepsis due to fungal organisms increased by 207 percent, with gram-positive bacteria becoming the predominant pathogens after 1987, and the total in-hospital mortality rate fell, yet the total number of deaths continued to increase.
Annual Review of ImmunologyFunction and Activation of NF-kappaB in the Immune System
4,698 Citations1994Patrick A. Baeuerle, Thomas Henkel
The inhibition of NF-kappa B activation by antioxidants and specific protease inhibitors may provide a pharmacological basis for interfering with these acute processes in suppressing toxic/septic shock, graft-vs-host reactions, acute inflammatory reactions, severe phase response, and radiation damage.
NatureRelease of chromatin protein HMGB1 by necrotic cells triggers inflammation
4,180 Citations2002Paola Scaffidi, Tom Misteli +1 more
It is reported that Hmgb1-/- necrotic cells have a greatly reduced ability to promote inflammation, which proves that the release of HMGB1 can signal the demise of a cell to its neighbours, and cells undergoing apoptosis are programmed to withhold the signal that is broadcast by cells that have been damaged or killed by trauma.
NatureVagus nerve stimulation attenuates the systemic inflammatory response to endotoxin
4,150 Citations2000L. V. Borovikova, Svetlana Ivanova +8 more
Direct electrical stimulation of the peripheral vagus nerve in vivo during lethal endotoxaemia in rats inhibited TNF synthesis in liver, attenuated peak serum TNF amounts, and prevented the development of shock.
New England Journal of MedicineThe Pathophysiology and Treatment of Sepsis
4,114 Citations2003Richard S. Hotchkiss, Irene E. Karl
This review examines evolving concepts of sepsis and discusses new and potential therapies, including therapy with activated protein C, stringent control of blood glucose, and early goal-directed therapy to treat cellular oxygen deficit.
Nature reviews. ImmunologyNF-κB regulation in the immune system
3,968 Citations2002Qiutang Li, Inder M. Verma
The role of NF-kappaB proteins as potential therapeutic targets in clinical applications and their role in the immune system and inflammatory diseases are discussed.
NatureThe inflammatory reflex
3,487 Citations2002Kevin J. Tracey
The discovery that cholinergic neurons inhibit acute inflammation has qualitatively expanded understanding of how the nervous system modulates immune responses, and the opportunity now exists to apply this insight to the treatment of inflammation through selective and reversible 'hard-wired' neural systems.
ScienceHMG-1 as a Late Mediator of Endotoxin Lethality in Mice
3,393 Citations1999Haichao Wang, Ona Bloom +17 more
High mobility group-1 (HMG-1) protein was found to be released by cultured macrophages more than 8 hours after stimulation with endotoxin, TNF, or IL-1, and showed increased serum levels after endotoxin exposure, suggesting that this protein warrants investigation as a therapeutic target.
NatureA protein kinase involved in the regulation of inflammatory cytokine biosynthesis
3,310 Citations1994John C. Lee, Jeffrey T. Laydon +16 more
Production of interleukin-1 and tumour necrosis factor from stimulated human monocytes is inhibited by a new series of pyridinyl-imidazole compounds, suggesting that the CSBPs are critical for cytokine production.
NatureNicotinic acetylcholine receptor α7 subunit is an essential regulator of inflammation
3,195 Citations2002Hong Wang, Man Yu +11 more
The nicotinic acetylcholine receptor alpha7 subunit is essential for inhibiting cytokine synthesis by the cholinergic anti-inflammatory pathway.
NatureCrystal structure of an ACh-binding protein reveals the ligand-binding domain of nicotinic receptors
1,750 Citations2001Katjuša Brejc, Willem J. van Dijk +5 more
The crystal structure of molluscan acetylcholine-binding protein (AChBP), a structural and functional homologue of the amino-terminal ligand-binding domain of an nAChR α-subunit, is presented and is relevant for the development of drugs against Alzheimer’s disease and nicotine addiction.
NatureGlutamate-mediated astrocyte–neuron signalling
1,733 Citations1994Vladimir Parpura, Trent A. Basarsky +4 more
Astrocytes regulate neuronal calcium levels through the calcium-dependent release of glutamate, and an NMDA (N-methyl-d-aspartate) receptor-mediated increase in neuronal calcium is demonstrated.
ScienceRole of Transcriptional Activation of IκBα in Mediation of Immunosuppression by Glucocorticoids
1,719 Citations1995Robert I. Scheinman, Patricia C. Cogswell +2 more
It is shown that the synthetic glucocorticoid dexamethasone induces the transcription of the IκBα gene, which results in an increased rate of Iκbα protein synthesis, which is predicted to markedly decrease cytokine secretion and thus effectively block the activation of the immune system.
ScienceIndependent Human MAP-Kinase Signal Transduction Pathways Defined by MEK and MKK Isoforms
1,563 Citations1995Benoît Dérijard, Joël Raingeaud +5 more
It is demonstrated that the activators of p38, MKK3 and MKK4, JNK (MKK4), and ERK (MEK1 and MEK2) define independent MAP kinase signal transduction pathways.
The Journal of Experimental MedicineHigh Mobility Group 1 Protein (Hmg-1) Stimulates Proinflammatory Cytokine Synthesis in Human Monocytes
1,410 Citations2000Ulf Andersson, Haichao Wang +9 more
Results indicate that, like other cytokine mediators of endotoxin lethality (e.g., TNF and IL-1), extracellular HMG-1 is a regulator of monocyte proinflammatory cytokine synthesis.
NatureStructure and gating mechanism of the acetylcholine receptor pore
1,269 Citations2003Atsuo Miyazawa, Yoshinori Fujiyoshi +1 more
An atomic model of the closed pore of the nicotinic acetylcholine receptor, obtained by electron microscopy of crystalline postsynaptic membranes, is presented.
The EMBO JournalMonocytic cells hyperacetylate chromatin protein HMGB1 to redirect it towards secretion
1,242 Citations2003Tiziana Bonaldi, Fabio Talamo +7 more
It is shown here that in all cells HMGB1 shuttles actively between the nucleus and cytoplasm, and secreted when monocytic cells receive an appropriate second signal.
Nature MedicineCholinergic agonists inhibit HMGB1 release and improve survival in experimental sepsis
1,174 Citations2004Hong Wang, Hong Liao +10 more
Proceedings of the National Academy of SciencesReversing established sepsis with antagonists of endogenous high-mobility group box 1
1,127 Citations2003Huan Yang, Mahendar Ochani +16 more
Observations demonstrate that specific inhibition of endogenous HMGB1 therapeutically reverses lethality of established sepsis indicating thatHMGB1 inhibitors can be administered in a clinically relevant time frame.
Annual Review of MedicineTUMOR NECROSIS FACTOR: A Pleiotropic Cytokine and Therapuetic Target
1,064 Citations1994Kevin J. Tracey, Anthony Cerami
The biology of TNF is discussed, with particular emphasis on its potential therapeutic role in septic shock and cachexia, which has recently been the focus of intensive research.
Progress in NeurobiologyNeuronal nicotinic receptors: from structure to pathology
962 Citations2004Cecilia Gotti, F. Clementi
This review will attempt to survey the major achievements reached in the study of the structure and function of NAChRs by examining their regional and cellular localisation and the molecular basis of their functional diversity mainly in pharmacological and biochemical terms.
JAMARecombinant human interleukin 1 receptor antagonist in the treatment of patients with sepsis syndrome. Results from a randomized, double-blind, placebo-controlled trial. Phase III rhIL-1ra Sepsis Syndrome Study Group
932 Citations1994Charles J. Fisher
Primary and retrospective analyses of efficacy suggest that treatment with rhIL-1ra results in a dose-related increase in survival time among patients with sepsis who have organ dysfunction and/or a predicted risk of mortality of 24% or greater.
Nature reviews. NeuroscienceEmerging structure of the Nicotinic Acetylcholine receptors
908 Citations2002Arthur Karlin
The conversion of acetylcholine binding into ion conduction across the membrane is becoming more clearly understood in terms of the structure of the receptor and its transitions.
NatureInhibition of transforming growth factor-β/SMAD signalling by the interferon-γ/STAT pathway
808 Citations1999Luis Ulloa, Jacqueline Doody +1 more
The results indicate a mechanism of transmodulation between the STAT and SMAD signal-transduction pathways that prevents the interaction of Smad3 with the TGF-β receptor.
Annual Review of Cell BiologyTumor Necrosis Factor, Other Cytokines and Disease
784 Citations1993Kevin J. Tracey, Anthony Cerami
Information is provided on how to identify the wood of several species common to the Northern Hemisphere using a hand-magnifying lens.
The FASEB JournalThe interleukin‐1 family: 10 years of discovery <sup>1</sup>
784 Citations1994Charles A. Dinarello
JAMARecombinant Human Interleukin 1 Receptor Antagonist in the Treatment of Patients With Sepsis Syndrome
779 Citations1994Charles J. Fisher
Primary and retrospective analyses of efficacy suggest that treatment with rhIL-1ra results in a dose-related increase in survival time among patients with sepsis who have organ dysfunction and/or a predicted risk of mortality of 24% or greater.
NeuronNicotine and Carbamylcholine Binding to Nicotinic Acetylcholine Receptors as Studied in AChBP Crystal Structures
775 Citations2004Patrick H. N. Celie, Sarah E. van Rossum-Fikkert +4 more
Atomic resolution structures of nicotine and carbamylcholine binding to AChBP, a water-soluble homolog of the ligand binding domain of nicotinic receptors and their family members, GABAA,GABAC, 5HT3 serotonin, and glycine receptors are presented.
Nature MedicineNovel strategies for the treatment of sepsis
774 Citations2003Niels C. Riedemann, Ren-Feng Guo +1 more
The history of therapeutic interventions in clinical trials for sepsis has been referred to as the “graveyard for pharmaceutical companies,” but that is set to change, as research provides hope for new approaches that will be therapeutically effective in humans withSepsis.
PubMedIntracellular calcium oscillations in astrocytes: a highly plastic, bidirectional form of communication between neurons and astrocytes in situ.
734 Citations1997Lucia Pasti, Andrea Volterra +2 more
Nature MedicineProtection from septic shock by neutralization of macrophage migration inhibitory factor
725 Citations2000Thierry Calandra, Bernd Echtenacher +8 more
It is reported here that macrophage migration inhibitory factor (MIF) is a critical mediator of septic shock and a new target for therapeutic intervention is identified.
ScienceNicotine Activation of α4* Receptors: Sufficient for Reward, Tolerance, and Sensitization
688 Citations2004Andrew R. Tapper, Sheri McKinney +8 more
Activation of α4* nicotinic acetylcholine receptors with low doses of agonist recapitulates nicotine effects thought to be important in dependence, including reinforcement in response to acute nicotine administration, as well as tolerance and sensitization elicited by chronic nicotine administration.
Nature reviews. ImmunologyDevelopment of anti-TNF therapy for rheumatoid arthritis
675 Citations2002Marc Feldmann
Progress in the characterization of intercellular mediators — proteins that are now known as cytokines — has led to the realization that one cytokine, tumour-necrosis factor (TNF; previously known as TNF-α), has an important role in the pathogenesis of rheumatoid arthritis.
Journal of NeuroscienceIntracellular Calcium Oscillations in Astrocytes: A Highly Plastic, Bidirectional Form of Communication between Neurons and Astrocytes<i>In Situ</i>
665 Citations1997Lucia Pasti, Andrea Volterra +2 more
It is shown here that stimulation of neuronal afferents triggered periodic [Ca2+]i oscillations in astrocytes, which represent a highly plastic signaling system that underlies the reciprocal communication between neurons and astroCytes.
PubMedDouble-blind randomised controlled trial of monoclonal antibody to human tumour necrosis factor in treatment of septic shock. NORASEPT II Study Group.
628 Citations1998Edward Abraham, Antonio Anzueto +17 more
The safety and efficacy of murine monoclonal antibody to human tumour necrosis factor alpha (TNF alpha MAb) in the treatment of septic shock is assessed and therapy not solely dependent on TNF alpha blockade may be required to improve survival.
Critical Care MedicineHas the mortality of septic shock changed with time?
609 Citations1998Gilberto Friedman, Eliezer Silva +1 more
There was an increasing prevalence of Gram-positive causative organisms, and a change of the predominant origin of sepsis from the abdomen to the chest, in patients with bacteremia as an entry criterion.
Proceedings of the National Academy of SciencesEthyl pyruvate prevents lethality in mice with established lethal sepsis and systemic inflammation
592 Citations2002Luis Ulloa, Mahendar Ochani +7 more
It is reported that EP attenuates lethal systemic inflammation caused by either endotoxemia or sepsis even if treatment begins after the early tumor necrosis factor response, and a new strategy to pharmacologically inhibit HMGB1 release with a small molecule that is effective at clinically achievable concentrations is described.
NatureA glia-derived acetylcholine-binding protein that modulates synaptic transmission
564 Citations2001August B. Smit, Naweed I. Syed +11 more
A molecular and cellular mechanism by which glial cells release AChBP in the synaptic cleft is described, and a model for how they actively regulate cholinergic transmission between neurons in the central nervous system is proposed.
Reviews of physiology, biochemistry and pharmacologyNicotinic acetylcholine receptors: from structure to brain function
530 Citations2003R. C. Hogg, M. Raggenbass +1 more
Functional studies have revealed that nAChRs contribute to the control of resting membrane potential, modulation of synaptic transmission and mediation of fast excitatory transmission.
Nature GeneticsThe lack of chromosomal protein Hmg1 does not disrupt cell growth but causes lethal hypoglycaemia in newborn mice
528 Citations1999Sabina Calogero, Fabio Grassi +5 more
The Journal of Experimental MedicinePharmacological Stimulation of the Cholinergic Antiinflammatory Pathway
522 Citations2002Thomas Bernik, Steven G. Friedman +8 more
Results indicate that stimulation of the cholinergic antiinflammatory pathway by either pharmacological or electrical methods can attenuate the systemic inflammatory response to endotoxin-induced shock.
Journal of Clinical InvestigationEpinephrine inhibits tumor necrosis factor-alpha and potentiates interleukin 10 production during human endotoxemia.
517 Citations1996Tom van der Poll, S M Coyle +3 more
Epinephrine, either endogenously produced or administered as a component of sepsis treatment, may have a net antiinflammatory effect on the cytokine network early in the course of systemic infection.
New England Journal of MedicineTransdermal Nicotine for Active Ulcerative Colitis
515 Citations1994Rupert Pullan, John Rhodes +9 more
The addition of transdermal nicotine to conventional maintenance therapy improves symptoms in patients with ulcerative colitis.
Journal of NeuroscienceMice Deficient in the α7 Neuronal Nicotinic Acetylcholine Receptor Lack α-Bungarotoxin Binding Sites and Hippocampal Fast Nicotinic Currents
499 Citations1997Avi Orr‐Urtreger, Finn M. Göldner +7 more
It is demonstrated that the α7 subunit is not essential for normal development or for apparently normal neurological function, but the mice may prove to have subtle phenotypic abnormalities and will be valuable in defining the functional role of this gene product in vivo.
The Journal of Experimental MedicineCholinergic stimulation blocks endothelial cell activation and leukocyte recruitment during inflammation
496 Citations2005Rubina W. Saeed, Santosh K. Varma +7 more
The LancetDouble-blind randomised controlled trial of monoclonal antibody to human tumour necrosis factor in treatment of septic shock
494 Citations1998Edward Abraham, Antonio Anzueto +17 more
It was found there was no association between therapy with TNFα MAb and increased rapidity in reversal of initial shock or prevention of subsequent shock, and baseline plasma interleukin-6 concentrations were not associated with improvement in survival after TNF α MAb therapy.
The Annual Review of Pharmacology and ToxicologyCatecholamine Influences and Sympathetic Neural Modulation of Immune Responsiveness
440 Citations1995Kelley S. Madden, V M Sanders +1 more
The importance of the sympathetic nervous system in modulating immune function under normal and disease states is illustrated and the role of chemical sympathectomy in this regard is illustrated.
Trends in Molecular MedicineThe ‘cytokine profile’: a code for sepsis
438 Citations2005Luis Ulloa, Kevin J. Tracey
It is proposed that the current definition of sepsis is too broad and encompasses heterogeneous groups of patients suffering similar, but different, syndromes that are historically grouped under the general diagnosis of septicaemia.
Journal of Clinical NeurophysiologyVagus Nerve Stimulation, Side Effects, and Long-Term Safety
387 Citations2001Elinor Ben‐Menachem
Vagus nerve stimulation is an accepted therapy for the treatment of refractory epilepsy and now even depression and this treatment option offers patients with refracted epilepsy prospects of good efficacy with only minor and often resolvable side effects.
Critical Care MedicineConsensus conference definitions for sepsis, septic shock, acute lung injury, and acute respiratory distress syndrome: Time for a reevaluation
372 Citations2000Edward Abraham, Michael A. Matthay +8 more
An important challenge is to progress from clinical syndromes to more specific entities that are delineated by alterations in specific immunologic or biochemical pathways, which will provide more homogeneous groups of patients who can be identified at early stages of their clinical course.
BMJNon-smoking: a feature of ulcerative colitis.
329 Citations1982Anthony Harries, Andrew Baird +1 more
CirculationEfferent Vagal Fibre Stimulation Blunts Nuclear Factor-κB Activation and Protects Against Hypovolemic Hemorrhagic Shock
319 Citations2003Salvatore Guarini, Domenica Altavilla +11 more
The results show a parasympathetic inhibition of NF-&kgr;B by which the brain opposes NF- &kGr;B activation in the liver and modulates the inflammatory response during acute hypovolemic hemorrhagic shock.
Autonomic NeuroscienceRole of vagus nerve signaling in CNI-1493-mediated suppression of acute inflammation
317 Citations2000L. V. Borovikova, Svetlana Ivanova +5 more
The Journal of Infectious DiseasesThe Cholinergic Anti‐Inflammatory Pathway Regulates the Host Response during Septic Peritonitis
311 Citations2005David J. van Westerloo, Ilona A. J. Giebelen +6 more
Evidence is provided of an important role of the vagus nerve in regulating the innate immune response to a severe bacterial infection, and the first evidence, to the authors' knowledge, of an important role of the vagus nerve in regulating the innate immune response to a severe bacterial infection.
Critical Care MedicineLenercept (p55 tumor necrosis factor receptor fusion protein) in severe sepsis and early septic shock: A randomized, double-blind, placebo-controlled, multicenter phase III trial with 1,342 patients
291 Citations2001Edward Abraham, Pierre-François Laterre +17 more
This phase III study confirmed a trend observed in a previous phase II study showing that a single dose of lenercept, human recombinant p55 tumor necrosis factor receptor-immunoglobulin G1 (TNFR55-IgG1) fusion protein, decreased mortality in patients with severe sepsis or early septic shock.
Journal of NeuroscienceBicuculline and Gabazine Are Allosteric Inhibitors of Channel Opening of the GABA<sub>A</sub>Receptor
262 Citations1997Shinya Ueno, John Bracamontes +3 more
Study of the ability of alphaxalone and pentobarbital to directly activate recombinant GABAA receptors containing the α1, β2, and γ2L subunits concludes that the sites for binding steroids and barbiturates do not overlap with the GABA-binding site.
GenomicsGenomic Organization and Partial Duplication of the Human α7 Neuronal Nicotinic Acetylcholine Receptor Gene (CHRNA7)
243 Citations1998Judith Gault, Misi Robinson +15 more
The human alpha7 neuronal nicotinic acetylcholine receptor gene (HGMW-approved symbol CHRNA7) has been characterized from genomic clones and four novel exons are described, located in genomic clones containing the partially duplicated gene.
NeuropsychopharmacologySafety, Pharmacokinetics, and Effects on Cognitive Function of Multiple Doses of GTS-21 in Healthy, Male Volunteers
235 Citations2002Harumi KITAGAWA, Toshiharu TAKENOUCHI +5 more
ShockTUMOR NECROSIS FACTOR IN SEPSIS: MEDIATOR OF MULTIPLE ORGAN FAILURE OR ESSENTIAL PART OF HOST DEFENSE?
231 Citations1995Tom van der Poll, Stephen F. Lowry
The current review addresses recent insights into the structure and function of this pleiotropic cytokine, with a particular emphasis upon cellular and organ system consequences of sepsis-induced TNF activity.
Molecular PharmacologyHuman alpha 7 acetylcholine receptor: cloning of the alpha 7 subunit from the SH-SY5Y cell line and determination of pharmacological properties of native receptors and functional alpha 7 homomers expressed in Xenopus oocytes.
222 Citations1994Xiao-ding Peng, M.D. Katz +3 more
Journal of NeuroscienceNeuronal α-Bungarotoxin Receptors Are α7 Subunit Homomers
217 Citations2000Renaldo C. Drisdel, William N. Green
Evidence is presented that α-bungarotoxin (Bgt)-binding nicotinic receptors found in pheochromocytoma 12 (PC12) cells are pentamers composed solely of α7 subunits.
Journal of NeurobiologyUnconventional ligands and modulators of nicotinic receptors
198 Citations2002Edna F. R. Pereira, Corey J. Hilmas +4 more
The present article reviews and discusses the effects of unconventional ligands on nAChR activity and briefly describes the potential benefits of using some of these compounds in the treatment of neuropathologic conditions in which nA ChR function/expression is known to be altered.
New England Journal of MedicineTransdermal Nicotine as Maintenance Therapy for Ulcerative Colitis
192 Citations1995Gareth Thomas, John Rhodes +5 more
Transdermal nicotine alone was no better than placebo in the maintenance of remission of ulcerative colitis, and premature withdrawal due to side effects was more common in the nicotine group.
Journal of Pharmacology and Experimental TherapeuticsEthyl Pyruvate Inhibits Nuclear Factor-κB-Dependent Signaling by Directly Targeting p65
152 Citations2005Yusheng Han, Joshua A. Englert +3 more
Some of the beneficial anti-inflammatory effects of ethyl pyruvate may be due to modification of p65, thereby inhibiting signaling via the NF-κB pathway.
Annual Review of Biophysics and Biomolecular StructureAcetylcholine Binding Protein (AChBP): A Secreted Glial Protein That Provides a High-Resolution Model for the Extracellular Domain of Pentameric Ligand-Gated Ion Channels
141 Citations2003Titia K. Sixma, August B. Smit
The crystal structure of AChBP provides the first high-resolution structure for this family of Cys-loop receptors and helps create models for toxin binding, mutational effects, and molecular gating.
Trends in ImmunologySmad7 in TGF-β-mediated negative regulation of gut inflammation
134 Citations2004Giovanni Monteleone, Francesco Pallone +1 more
This work delineates a scenario in which the high expression of Smad7 in inflammatory cells renders them unresponsive to TGF-β1 and proposes that control ofSmad7, not TGF -β1 production, is a key determinant in understanding how TGF,β1 negatively regulates gut inflammation.
Cardiovascular ResearchAdrenocorticotropin reverses hemorrhagic shock in anesthetized rats through the rapid activation of a vagal anti-inflammatory pathway
131 Citations2004Salvatore Guarini
The present data show, for the first time, that the melanocortin ACTH-(1-24) suppresses the NF-kappaB-dependent systemic inflammatory response triggered by hemorrhage, and reverses shock condition, by brain activation (in real-time) of the "cholinergic anti-inflammatory pathway", this pathway seeming to be melanoc Cortin-dependent.
Journal of Pharmacology and Experimental TherapeuticsAnalysis of 3-(4-Hydroxy, 2-Methoxybenzylidene)Anabaseine Selectivity and Activity at Human and Rat Alpha-7 Nicotinic Receptors
130 Citations1998Edwin M. Meyer, Alexander Kuryatov +3 more
The studies suggest that the efficacy of GTS-21 in primates may depend on a pro-drug function, and 4OH-G TS-21 was protective in both human and rat cell lines, although GTS -21 was effective only in the latter.
BMJSmoking and ulcerative colitis.
124 Citations1984RF Logan, M Edmond +2 more
It is suggested that smoking directly or indirectly confers protection against ulcerative colitis and could be explained by confounding by social class.
DigestionTime Relationships between Cessation of Smoking and Onset of Ulcerative Colitis
124 Citations2009Richard Motley, John Rhodes +6 more
It is suggested that smoking exerts protective effect against the development of ulcerative colitis.
Biochemical and Biophysical Research CommunicationsNicotine Inhibits the Production of Inflammatory Mediators in U937 Cells through Modulation of Nuclear Factor-kB Activation
115 Citations1998Naoyuki Sugano, Koichi Shimada +2 more
Pretreatment with nicotine caused a significant inhibition of LPS-induced IL-1, IL-8, and PGE2 expression at the transcriptional level in U937 cells, which may contribute to cigarette smoke-induced immunosuppression.
NatureA nervous connection
96 Citations2003Claude Libert
The molecular details of a connection between the nervous system and the inflammatory response to disease have been uncovered and suggest new avenues of research into controlling excessive inflammation.
Journal of Biological ChemistryProtein Kinase CK2 Differentially Phosphorylates Maize Chromosomal High Mobility Group B (HMGB) Proteins Modulating Their Stability and DNA Interactions
91 Citations2002Christian Stemmer, Andrea Schwander +3 more
Findings show that phosphorylation of residues within the acidic C-terminal domain of the HMGB proteins can modulate protein stability and the DNA binding properties of theHMGB proteins.
Journal of NeuroimmunologyExpression of an α7 duplicate nicotinic acetylcholine receptor-related protein in human leukocytes
90 Citations2002Y. Villiger, Ildikó Szántó +6 more
Data indicate that leukocytes express in their membrane the dupalpha7 protein but its physiological role remains to be identified.
Scandinavian Journal of GastroenterologySmoking Habits in Patients with Inflammatory Bowel Disease
88 Citations1984Cecilia Benoni, Å. Nilsson
The proportion of smokers in this study was significantly lower among Patients with ulcerative colitis than among patients with Crohn's disease, the difference being significant for both sexes and for the age groups both below and above 40 years.
Arthritis & RheumatismHigh mobility group box chromosomal protein 1 as a nuclear protein, cytokine, and potential therapeutic target in arthritis
87 Citations2003Luis Ulloa, Franak Batliwalla +3 more
The history of research on HMGB-1 as an intracellular protein is summarized and a rapidly growing body of evidence that implicates HMGB -1 as a cytokine that can mediate inflammation and arthritis is discussed.
GutEffect of nicotine on rectal mucus and mucosal eicosanoids.
84 Citations1994Freek J. Zijlstra, E D Srivastava +8 more
Prostaglandins (PG) were reduced, in some cases significantly (6-keto PGF1 alpha, PGF2 alpha, and hydroxy-eicosatetraenoic acid), by nicotine, which showed an inverse dose dependence--with greatest inhibition in relation to the lowest dose.
Current Medicinal ChemistryRole of Cytokines in Neurological Disorders
75 Citations2003Johan A. Aarli
The balance between cytokines with pro- and anti-inflammatory effects contributes to the course of the Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy and studies of patients with epilepsy and animals with experimentally induced seizures indicate that cytokines may also influence the electrophysiological properties of neurons.
Molecular PharmacologyRegulation of Nicotinic Acetylcholine Receptor Channel Function by Acetylcholinesterase Inhibitors in Rat Hippocampal CA1 Interneurons
72 Citations2004Dmitriy Fayuk, Jerrel L. Yakel
Drugs that target AChE are likely to be important regulators of cholinergic signaling in the hippocampus, with no effect on the levels of choline or carbachol.
Science s STKEAt the Crossroads of Necrosis and Apoptosis: Signaling to Multiple Cellular Targets by HMGB1
72 Citations2002Michael Bustin
How the mobility of the nuclear protein high mobility group B1 (HMGB1) may be a key signal for determining whether certain cells undergo necrotic or apoptotic death is discussed.
Behavioural Brain ResearchAltered baroreflex responses in α7 deficient mice
67 Citations2000Davide Franceschini, Avi Orr‐Urtreger +7 more
It is shown that the α7 null mice have impaired sympathetic responses to vasodilatation, and the decreased baroreflex-mediated tachycardia in α7 mutant mice indicates that α7-containing nAChRs participate in the autonomic reflex that maintains blood pressure homeostasis.
BMJNon-smoking: a feature of ulcerative colitis.
65 Citations1982H Castella
The high values reported by Dr Elwood and others for village children from North Wales could reflect the fact that the naturally acid water would tend to solubilise this element from both lead pipes and rocks.
Expert Opinion on Investigational DrugsAnti-TNF agents in Crohn’s disease
62 Citations2000Gert Van Assche, Paul Rutgeerts
Although there are some concerns about immunogenicity of the anti-TNF antibody resulting in the formation of human antichimeric antibodies (HACA) as well as lymphoproliferative disorders, the clinical benefit in the treatment of refractory Crohn’s disease is a major therapeutic breakthrough.
European Journal of PharmacologyNicotinic acetylcholine receptor knockout mice as animal models for studying receptor function
56 Citations2000Lisa M. Marubio, Jean‐Pierre Changeux
This review focuses on how the study of knockout mouse models has advanced understanding of the role individual nicotinic acetylcholine receptor subunits play in the function and composition of endogenous receptors and the diverse pharmacological actions of nicotine in the mammalian nervous system.
International Journal of Colorectal DiseaseLate presentation of ulcerative colitis in ex-smokers
55 Citations1988Richard Motley, J. Rhodes +2 more
It is suggested that whilst current smokers may have a lower incidence of colitis, ex-smokers appear to be at increased risk of developing the disease.
Nature MedicineCan nicotine treat sepsis?
51 Citations2004Michael A. Matthay, Lorraine B. Ware
The acetylcholine receptor modulates interactions between the nervous system and the immune system, and is now harnessed to dampen inflammation and reduce mortality in a mouse model of sepsis.
European Journal of NeurosciencePotentiation of evoked calcitonin gene‐related peptide release from oral mucosa: a potential basis for the pro‐inflammatory effects of nicotine
50 Citations2003Gregory Dussor, Anthony S.‐Y. Leong +5 more
The hypothesis that nicotinic agents, acting at nAChRs contained on primary sensory neurons, are capable of directly modulating the stimulated release of iCGRP is supported.
Journal of NeuroscienceGalantamine Activates Muscle-Type Nicotinic Acetylcholine Receptors without Binding to the Acetylcholine-Binding Site
46 Citations2005Gustav Akk, Joe Henry Steinbach
Galantamine activates the muscle-type ACh receptor by interacting with a binding site that is distinct from the site for nicotinic agonists, and does not interfere with the occupation of the nicotinics agonist binding site by ACh, carbachol, or choline.
Current Pharmaceutical DesignAnti - TNF Therapy for Crohns Disease
42 Citations2003Geert D’Haens
The exciting "TNF story" very nicely illustrates how the benchmark of basic immunological research now provides us with very potent and rationally designed drugs.
Neuroscience ResearchPlasticity of spinal nicotinic acetylcholine receptors following spinal nerve ligation
37 Citations2003Michelle Vincler, James C. Eisenach
It is proposed that the increased expression of the alpha3 and alpha5 nicotinic subunits may contribute to the mechanical hypersensitivity observed following spinal nerve ligation.
European Journal of PharmacologyPharmacology of the nicotinic acetylcholine receptor from fetal rat muscle expressed in Xenopus oocytes
36 Citations1996Julia C. Cooper, Oliver Gutbrod +2 more
The fetal rat muscle nicotinic acetylcholine receptor was expressed in Xenopus oocytes using the voltage-clamp technique and the agonist responses were compared with the steric and electrostatic properties of the molecules, using molecular modelling.
NeuroreportA conus peptide blocks nicotinic receptors of unmyelinated axons in human nerves
30 Citations2005Philip M. Lang, Ralf Burgstahler +3 more
Vc1.1 in concentrations above 0.1 μM antagonized the increase in axonal excitability produced by nicotine and demonstrated immunoreactivity for &agr;3 and &agR;5 subunits of neuronal nicotinic receptors on unmyelinated peripheral human axons, which may be helpful in painful neuropathies affecting un myelinated sympathetic and/or sensory axons.
Pharmacology Biochemistry and BehaviorKnock down of the ?5 nicotinic acetylcholine receptor in spinal nerve-ligated rats alleviates mechanical allodynia
27 Citations2004Michelle Vincler, James C. Eisenach
The results suggest that the increased expression of the alpha5 nAChR subunit following SNL contributes to spinal CREB phosphorylation and the maintenance of mechanical allodynia.
Nature MedicineInfectious triggers for inflammatory neurological diseases
27 Citations2002Kai W. Wucherpfennig
A new study provides strong evidence for a virus-induced autoimmune process in a human neurological disease.
Nature MedicineMIF mediation of sepsis
27 Citations2000Thomas R. Martin
The individual searches for a natural antagonist of cortisol and for critical mediators of sepsis have converged in the finding that MIF is an important mediator of septic shock.
Nature MedicineTangling with hypothermia
27 Citations2004Jesús Ávila, Javier Díaz‐Nido
Hypothermia resulting from impaired glucose metabolism may be one of the factors that contribute to hyperphosphorylation of the protein tau and subsequent neuronal dysfunction.
Annals of Internal MedicineTransdermal Nicotine for Ulcerative Colitis
24 Citations1997Yukio Ando
It is feared that the small quality-of-life benefit may not compensate for the latent risk for cancer in patients with such benign disease and chronic effects by an intensive exposure to nicotine should be carefully assessed before patients received nicotine therapy in clinical practice.
GutIn vitro mucus glycoprotein production by colonic tissue from patients with ulcerative colitis.
22 Citations1988G F Cope, R V Heatley +2 more
The results indicate that the quantitative character of colonic mucus is abnormal in inactive ulcerative colitis.
…