Ozone-induced lung inflammation and hyperreactivity are mediated via tumor necrosis factor-α receptors
American Journal of Physiology-Lung Cellular and Molecular PhysiologyPublished 1 March 2001
Hye‐Youn Cho, Liuyi Zhang, Steven R. Kleeberger
Citations158
SJR quartileQ1
SJR score1.24
SNIP0.85
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TL;DR
A critical role for TNFR signaling is suggested in subacute O(3)-induced pulmonary epithelial injury and inflammation and in acute O( 3)-induced airway hyperreactivity in knockout mice.
Abstract
This study was designed to investigate the mechanisms through which tumor necrosis factor (Tnf) modulates ozone (O(3))-induced pulmonary injury in susceptible C57BL/6J (B6) mice. B6 [wild-type (wt)] mice and B6 mice with targeted disruption (knockout) of the genes for the p55 TNF receptor [TNFR1(-/-)], the p75 TNF receptor [TNFR2(-/-)], or both receptors [TNFR1/TNFR2(-/-)] were exposed to 0.3 parts/million O(3) for 48 h (subacute), and lung responses were determined by bronchoalveolar lavage. All TNFR(-/-) mice had significantly less O(3)-induced inflammation and epithelial damage but not lung hyperpermeability than wt mice. Compared with air-exposed control mice, O(3) elicited upregulation of lung TNFR1 and TNFR2 mRNAs in wt mice and downregulated TNFR1 and TNFR2 mRNAs in TNFR2(-/-) and TNFR1(-/-) mice, respectively. Airway hyperreactivity induced by acute O(3) exposure (2 parts/million for 3 h) was diminished in knockout mice compared with that in wt mice, although lung inflammation and permeability remained elevated. Results suggested a critical role for TNFR signaling in subacute O(3)-induced pulmonary epithelial injury and inflammation and in acute O(3)-induced airway hyperreactivity.
Keywords
MedicineEnvironmental Science
Analytical BiochemistrySingle-Step Method of RNA Isolation by Acid Guanidinium Thiocyanate–Phenol–Chloroform Extraction
63,238 Citations1987Piotr Chomczynski
Analytical BiochemistrySingle-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction
46,819 Citations1987Piotr Chomczyński, Nicoletta Sacchi
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New England Journal of MedicineThe Tumor Necrosis Factor Ligand and Receptor Families
1,235 Citations1996Flavia Bazzoni, Bruce Beutler
Tumor necrosis factor and lymphotoxin-α were isolated more than 10 years ago on the basis of their ability to kill tumor cells in vitro and to cause hemorrhagic necrosis of transplantable tumors in mice, and a factor known as cachectin was isolated from mouse macrophages, sequenced, and shown to be identical to TNF.
American Journal of Respiratory and Critical Care MedicineHealth Effects of Outdoor Air Pollution. Part 2. Committee of the Environmental and Occupational Health Assembly of the American Thoracic Society
877 Citations1996
Although sources of airborne lead have been reduced over the last decade, there are still relatively high levels of lead contamination in soils and the residential housing stock built before the 1970s, which pose a risk for continued direct exposure through ingestion or airborne exposure if resuspended.
Trends in Cell BiologyTwo tumour necrosis factor receptors: structure and function
795 Citations1995Peter Vandenabeele, Wim Declercq +2 more
Tumour necrosis factor induces receptor oligomerization, an event that is believed to connect the receptors to downstream signalling pathways, and suggests that several TNF-R-associated proteins may initiate cytoplasmic signal transduction.
The Journal of ImmunologyTNF Receptor-Deficient Mice Reveal Divergent Roles for p55 and p75 in Several Models of Inflammation
708 Citations1998Jacques J. Peschon, Dauphine Torrance +8 more
The biologic roles of p55 and p75 in mediating and modulating the biologic activity of TNF are clarified and genetic evidence for an antagonistic role of p75 is provided in vivo.
American Journal of Respiratory and Critical Care MedicineHealth Effects of Outdoor Air Pollution. Committee of the Environmental and Occupational Health Assembly of the American Thoracic Society
677 Citations1996
This review suggests that the epidemiologic studies of adverse morbidity measures are coherent with the mortality studies showing quantitatively similar adverse effects of acute exposures to particulate pollution.
Proceedings of the National Academy of SciencesCloning and expression of cDNAs for two distinct murine tumor necrosis factor receptors demonstrate one receptor is species specific.
571 Citations1991Martyn Lewis, Louis A. Tartaglia +6 more
MTNF-R2 showed strong specificity for recombinant murine TNF-alpha, suggesting that the various activities of human tumor necrosis factor alpha reported in mice or in murine cell lines are probably mediated by mT NF-R1.
The Journal of ImmunologyInhibition of Lipopolysaccharide-Induced Signal Transduction in Endotoxin-Tolerized Mouse Macrophages: Dysregulation of Cytokine, Chemokine, and Toll-Like Receptor 2 and 4 Gene Expression
513 Citations2000Andrei E. Medvedev, Karen M. Kopydlowski +1 more
Understanding of LPS-signaling mechanisms that are inhibited in endotoxin-tolerized macrophages are extended and suggest that endotoxin tolerance might result from impaired expression and/or functions of common signaling intermediates involved in LPS and IL-1 signaling.
American Journal of Respiratory Cell and Molecular BiologyExposure of Humans to Ambient Levels of Ozone for 6.6 Hours Causes Cellular and Biochemical Changes in the Lung
475 Citations1991Robert B. Devlin, William F. McDonnell +5 more
Exposure of humans to as low a level as 0.08 ppm for 6.6 h is sufficient to initiate an inflammatory reaction in the lung, and exposure to 0.10 ppm ozone resulted in significant increases in PMNs, PGE2, LDH, IL-6, alpha 1-antitrypsin, and decreased phagocytosis via the complement receptor.
American Journal of Respiratory and Critical Care MedicineTumor Necrosis Factor-Alpha Increases Airway Responsiveness and Sputum Neutrophilia in Normal Human Subjects
358 Citations1995P S Thomas, Diana Yates +1 more
It is concluded that TNF alpha can induce an increase in airway responsiveness in normal subjects, and is associated with a neutrophil infiltration, thus making it a candidate cytokine for the induction of airway inflammation and hyperresponsiveness.
The Journal of ImmunologyStimulation of human T-cell proliferation by specific activation of the 75-kDa tumor necrosis factor receptor.
291 Citations1993Louis A. Tartaglia, David V. Goeddel +5 more
TNF-alpha can enhance the proliferation of human thymocytes stimulated by the comitogen Con A, and Lymphotoxin was also shown to stimulatehuman thymocyte proliferation, demonstrating that TNF-beta can initiate a biologic response that is mediated by T NF-R2.
American Review of Respiratory DiseaseTumor Necrosis Factor Causes Bronchial Hyperresponsiveness in Rats
287 Citations1992Johan Kips, Jan Tavernier +1 more
It is concluded that TNF causes bronchial hyperresponsiveness and airway inflammation.
PubMedAccurate quantification of cells recovered by bronchoalveolar lavage.
198 Citations1984Cesare Saltini, Allan J. Hance +4 more
Procedures for determining differential cell counts on lavage cells collected on Millipore filters and stained with hematoxylin-eosin were developed and the results of differential cell count performed on filter preparations with those obtained using cytocentrifuge preparations were compared.
Nature GeneticsLinkage analysis of susceptibility to ozone-induced lung inflammation in inbred mice
182 Citations1997Steven R. Kleeberger, Roy C. Levitt +7 more
Results strongly support linkage of O3 susceptibility to a QTL on chromosome 17 and Tnf as a candidate gene, the gene encoding the pro-inflammatory cytokine tumour necrosis factor-α(Tnf), which significantly protected against O3 injury in susceptible mice.
American Journal of Respiratory and Critical Care MedicineGreater Ozone-Induced Inflammatory Responses in Subjects With Asthma
175 Citations1996C Scannell, L Chen +7 more
The results indicate that asthmatic persons may be at risk of developing more severe O3-induced respiratory tract injury/inflammation than normal persons, and may help explain the increased asthma morbidity associated with O3 pollution episodes observed in epidemiologic studies.
American Journal of Respiratory Cell and Molecular BiologyGenetic Susceptibility to Ozone-Induced Lung Hyperpermeability: Role of Toll-Like Receptor 4
164 Citations2000Steven R. Kleeberger, Sekhar P. Reddy +2 more
Results indicate that a QTL on mouse chromosome 4 explains a significant portion of the genetic variance in O(3)-induced hyperpermeability, and support a role for Tlr4 as a strong candidate susceptibility gene.
The Journal of Experimental MedicineMonoclonal antibodies specific for murine p55 and p75 tumor necrosis factor receptors: identification of a novel in vivo role for p75.
162 Citations1995Kathleen C. F. Sheehan, J. Keith Pinckard +4 more
P55- but not p75- specific mAbs protected mice from lethal endotoxin shock and blocked development of a protective response against Listeria monocytogenes infection and identified a novel function of the p75 TNF receptor in vivo.
American Journal of Respiratory and Critical Care MedicineOzone-Induced Decrements in FEV1 and FVC Do Not Correlate With Measures of Inflammation
161 Citations1996John R. Balmes, L L Chen +6 more
Levels of O3-induced symptoms and respiratory tract injury/inflammation were not correlated with the magnitude of decrements in FEV1 and FVC, and there were no significant differences, however, between least- and most-sensitive groups.
Journal of Toxicology and Environmental Health Part BOZONE-INDUCED LUNG INFLAMMATION AND MUCOSAL BARRIER DISRUPTION: TOXICOLOGY, MECHANISMS, AND IMPLICATIONS
153 Citations1999D. K. Bhalla
The mucosal barrier functions in the lung is introduced, inflammatory and permeability consequences of O3 are evaluated, mechanisms of inflammatory reactions are addressed, and alternate viewpoints are offered.
The EMBO JournalDissociation of TNF‐alpha cytotoxic and proinflammatory activities by p55 receptor‐ and p75 receptor‐selective TNF‐alpha mutants.
144 Citations1994J. A. J. Barbara, William Smith +7 more
It is shown here that these two major activities of TNF‐alpha can be dissociated, with TNFR55‐selective mutants exhibited lower proinflammatory activity than wild‐type TNF.
Nature GeneticsGenetic analysis of ozone-induced acute lung injury in sensitive and resistant strains of mice
125 Citations1997Daniel R. Prows, Howard G. Shertzer +3 more
The findings implicate various genetic and epigenetic factors in individual susceptibility to air pollution in inbred mice and suggest that genetic determinants may control predisposition to the harmful effects of ozone.
American Journal of Respiratory Cell and Molecular BiologyUpregulation of the p75 But Not the p55 TNF-α Receptor mRNA after Silica and Bleomycin Exposure and Protection from Lung Injury in Double Receptor Knockout Mice
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The concept that TNF is a central mediator of interstitial pulmonary fibrosis is supported, with significant increases caused by silica in the C57BL/6, BALB/c, and 129/J mice, while hydroxyproline content of the lungs after treatment followed this same pattern.
American Journal of Respiratory and Critical Care MedicineOzone-induced Airway Inflammatory Changes Differ between Individuals and Are Reproducible
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It is demonstrated that inflammatory and lung function responses to ozone differ between individuals and are reproducible but not related to each other.
Journal of Applied PhysiologyAutosomal recessive inheritance of airway hyperreactivity to 5-hydroxytryptamine
112 Citations1989Roy C. Levitt, Wayne Mitzner
Linkage studies are reported which suggest that these genes are not closely linked and that 5-HT and ACh airway hyperresponsiveness is inherited independently and the results of these studies suggest that murine nonspecificAirway hyper Responsiveness is determined by multiple genes.
American Journal of Respiratory Cell and Molecular BiologyOzone Stimulates Synthesis of Inflammatory Cytokines by Alveolar Macrophages In Vitro
98 Citations1995K. Arsalane, Philippe Gosset +5 more
In the present study, the in vitro effect of low concentrations of O3 (0.1 to 1 ppm) was evaluated on cell viability and cytokine secretion by alveolar macrophages (AM) from guinea pigs and healthy subjects.
American Journal of Physiology-Lung Cellular and Molecular PhysiologyA genetic model for evaluation of susceptibility to ozone-induced inflammation
91 Citations1990Steven R. Kleeberger, David Bassett +2 more
The phenotypes of inbred mice and progeny of crosses between B6 and C3 strains were consistent with the hypothesis that a single autosomal recessive gene at the Inf locus confers susceptibility to acute O3-induced influx of PMNs, but the genetic control of altered permeability is not clear.
American Journal of Respiratory Cell and Molecular BiologySignal Transduction Pathways of Apoptosis and Inflammation Induced by the Tumor Necrosis Factor Receptor Family
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American Journal of Respiratory and Critical Care MedicineResponse to Acute Ozone Exposure in Healthy Men. Results of a Screening Procedure
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The results confirm the wide variability in spirometric responsiveness among individuals to O3 and suggest that intrinsic narrowing of the small airways may be a significant component of the functional response.
American Journal of Respiratory and Critical Care MedicineAirway Inflammation in Smokers and Nonsmokers with Varying Responsiveness to Ozone
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It is concluded that ozone-induced airway inflammation is independent of smoking status or airway responsiveness to ozone, and correlated with the late increase in PMN.
Journal of Applied PhysiologyOzone-induced hyperresponsiveness and blockade of M<sub>2</sub> muscarinic receptors by eosinophil major basic protein
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Data show that loss of neuronal M(2) receptor function after ozone is due to release of eosinophil MBP, and that function was acutely restored by removal of MBP with heparin.
Experimental Lung ResearchDifferential Susceptibility to Ozone-Induced Airways Hyperreactivity in Inbred Strains of Mice
60 Citations1995Liuyi Zhang, Roy C. Levitt +1 more
O3-induced ACh hyperreactivity was not a function of baseline reactivity, but correlated with susceptibility to acute O2-induced airways injury and inflammation, and Pharmacologic studies suggest that although PMNs were associated with O3- induced hyperreactive, these cells were not the cause of the effect, and that these two events are not codependent.
Journal of Applied PhysiologyAcute ozone-induced change in airway permeability: role of infiltrating leukocytes
55 Citations1992Steven R. Kleeberger, Bonnie B. Hudak
The experiments suggest that the influx of PMNs and the change in total BAL protein are not mutually dependent events in this model and suggest that infiltrating PMNs do not play a major role in acute O3-induced changes in permeability of the murine lung.
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The results suggest that endogenous NO may play an important role in the persistent airway inflammation and hyperresponsiveness after ozone exposure, presumably partly through the upregulation of IL-8.
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50 Citations1995Yoshinori Ohtsuka, M. Munakata +5 more
The results suggest that ozone-sensitive C57BL/6J mice are also more susceptible to silicosis than are ozone-resistant C3H/HeJ mice, and that the initial lower cellular responses and increase in TNF-alpha production may be related to the higher level of inflammatory and fibrotic response in the C57bl/ 6J mice.
Archives of Environmental Health An International JournalSusceptibility of Inbred Mouse Strains to Ozone
50 Citations1973Bernard D. Goldstein, Leslie Y. Lai +2 more
Inbred strains of mice vary greatly in their response to lethal levels of the oxidant air pollutant ozone, and it is suggested that this variation in susceptibility is inherited as a dominant characteristic.
American Journal of Physiology-Lung Cellular and Molecular PhysiologySusceptibility to ozone-induced inflammation. II. Separate loci control responses to acute and subacute exposures
47 Citations1993Steven R. Kleeberger, Roy C. Levitt +1 more
It is hypothesized that the same gene controls susceptibility to the airway inflammatory responses to 2 ppm and 0.30 ppm ozone exposures, and airway inflammation was induced in 10 BXH and 16 BXD recombinant inbred (RI) strains of mice by acute as well as subacute O3 exposures.
Journal of Applied PhysiologyOzone-induced loss of neuronal M2 muscarinic receptor function is prevented by cyclophosphamide
38 Citations1994L. M. Gambone, C L Elbon +1 more
The data suggest that ozone-induced loss of neuronal muscarinic receptor function is mediated via inflammatory cells and that the link between ozone- induced hyperresponsiveness and inflammation may be the neuronal M2 mus carinic receptor.
Toxicology LettersRole of inflammatory cytokines and nitric oxide in hepatic and pulmonary toxicity
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It is found that alveolar macrophages are activated to release the proinflammatory cytokine tumor necrosis factor-alpha (TNF alpha) which has been implicated in tissue injury and this response is time-dependent and correlated with expression of inducible nitric oxide synthase (NOS II) protein and mRNA.
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The hypothesis that O3-induced airways inflammation and epithelial damage in mice are partially mediated by activation of PAF receptors, possibly through modulation of ICAM-1 expression is supported.
PharmacogeneticsIntersubject variability in human acute ozone responsiveness
34 Citations1991William F. McDonnell
American Journal of Physiology-Lung Cellular and Molecular PhysiologyAblation of tumor necrosis factor receptor type I (p55) alters oxygen-induced lung injury
32 Citations2000Gloria Pryhuber, David O’Brien +5 more
The prediction that therapeutic efforts to block TNF-alpha receptor function will not protect against pulmonary oxygen toxicity is supported, and differences in early survival and toxicity suggest that pulmonary oxygenoxicity is in part mediated by TNFR-I.
Journal of Toxicology and Environmental HealthEFFECTS OF OZONE ON MACROPHAGE ADHESION IN VITRO AND EPITHELIAL AND INFLAMMATORY RESPONSES IN VIVO: THE ROLE OF CYTOKINES
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It was concluded that O3 affects the early stages of the inflammatory response, particularly with respect to macrophage activation and adherence to epithelial cells, and that this early response may be mediated by IL-1 alpha and/or TNF-alpha.
European Respiratory JournalAmbient ozone concentrations induce airway hyperresponsiveness in some rat strains
21 Citations1999Pieter Depuydt, Guy Joos +1 more
Investigation of the effect of a single low-level ozone exposure on different inbred rat strains found exposure to an ambient concentration of ozone induced airway hyperresponsiveness without airway inflammation in some highly inbreeding rat strains.
ToxicologyThe influence of polymorphonuclear leukocytes on altered pulmonary epithelial permeability during ozone exposure
16 Citations1998Paul G. Reinhart, David Bassett +1 more
It is suggested that a simple elevation in PMN number in the air spaces, as that induced by serum instillation, does not necessarily augment the lung pathophysiology, but that a more complex interaction with O3 may be required for cellular activation and release of toxic products.
European Journal of Pharmacology Environmental Toxicology and PharmacologyPlatelet-activating factor mediates the ozone-induced increase in airway microvascular leakage in guinea pigs
15 Citations1995Takeshi Kaneko, Hirotada Ikeda +3 more
It is suggested that PAF may be involved in ozone-induced airway inflammation after the effect of a PAF receptor antagonist significantly reduced the ozone- induced increase in microvascular leakage in a dose-dependent manner in both the trachea and main bronchi.
Journal of Applied PhysiologyMass cells contribute to O3-induced epithelial damage and proliferation in nasal and bronchial airways of mice
15 Citations1996Malinda Longphre, L. Y. Zhang +2 more
Testing the hypothesis that mast cells contribute to inflammation, epithelial sloughing, and epithelial proliferation in the nasal and terminal bronchiolar murine airways after O3 exposure found that these observations are consistent with the hypothesis That mast cells significantly modulate the inflammatory and proliferative responses of the murineAirways to O3.