Modulation of Lipopolysaccharide-Induced Gene Transcription and Promotion of Lung Injury by Mechanical Ventilation

Altemeier, William A.; Matute-Bello, Gustavo; Gharib, Sina A.; Glenny, Robb W.; Martin, Thomas R.; Liles, W. Conrad

doi:10.4049/jimmunol.175.5.3369

Cited by 138 publications

(139 citation statements)

References 40 publications

(28 reference statements)

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“…For in vivo experiments, mice were briefly anesthetized with isoflurane, and either mAb Jo-2 or isotype control antibody (2.5 μg/gm body weight) was administered by oropharyngeal aspiration as previously described [26]. Mice were returned to their cage to recover with free access to food and water.…”

Section: Fas Activationmentioning

confidence: 99%

Fas (CD95) induces macrophage proinflammatory chemokine production via a MyD88-dependent, caspase-independent pathway

Altemeier

Zhu

Berrington

et al. 2007

Journal of Leukocyte Biology

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Activation of the prototypical death receptor, Fas (CD95), can induce both caspase-dependent cell death and production of pro-inflammatory chemokines, leading to neutrophil recruitment and endorgan injury. The precise mechanism(s), by which Fas upregulates chemokine production and release, is currently unclear. We hypothesized that Fas-induced chemokine release by macrophages is dependent on the MyD88 adapter molecule and independent of caspase activity. To test this hypothesis, we measured chemokine response to Fas activation both in RAW 264.7 cells with RNAi-attenuated MyD88 expression and in MyD88-deficient primary macrophages. We found that Fas-induced chemokine release was abrogated in the absence of MyD88. In vivo, MyD88 −/− mice had impaired CXCL1/KC release and polymorphonuclear cell recruitment in response to intratracheal treatment with the Fas-activating monoclonal antibody, Jo-2. Furthermore, Fas-induced chemokine release was not dependent on either IL-1 receptor signaling or on caspase activity. We conclude that MyD88 plays an integral role in Fas-induced macrophage-mediated inflammation.

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Section: Fas Activationmentioning

confidence: 99%

Fas (CD95) induces macrophage proinflammatory chemokine production via a MyD88-dependent, caspase-independent pathway

Altemeier

Zhu

Berrington

et al. 2007

Journal of Leukocyte Biology

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“…Moderate tidal volume mechanical ventilation (MTV) has been reported to function as a cofactor in the initiation of acute lung injury (ALI) by amplifying the inflammatory response induced by pathogens (4,5). A study by Chun CD et al (6) found that mechanical ventilation at 10 ml/kg for 6 h in mice augmented poly(I:C)-induced cytokine release, polymorphonuclear (PMN) counts, 70-kD fluorescein isothiocyanate dextran concentration, and IgM level in bronchoalveolar lavage fluid (BALF).…”

mentioning

confidence: 99%

Mechanical Ventilation Augments Poly(I:C)-Induced Lung Injury via a WISP1-Integrin β3-Dependent Pathway in Mice

Jin

Chen

Ding

et al. 2016

Mol Med

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Mechanical ventilation can improve hypoxemia, but can also cause the so-called ventilator-induced lung injury (VILI). Polyinosinic:polycytidylic acid (poly(I:C)), an analogue of natural double-strand RNA virus, can induce lung inflammation. The purpose of this study was to determine whether moderate tidal volume mechanical ventilation (MTV) augments poly(I:C)-induced lung injury, and if so, the mechanism responsible for it. Two μg/g poly(I:C) were instilled intratracheally in C57BL/6J wide type (WT) mice. They were then randomized to MTV (10 ml/kg tidal volume) or spontaneous breathing. Lung tissues and bronchoalveolar lavage fluid (BALF) were collected 4 h later for various measurements. Our results showed that MTV did not cause significant injury in normal lungs, but augmented poly(I:C)-induced lung injury. The expression level of WNT-induced secreted protein 1 (WISP1) was consistent with lung injury, and the amplification of lung injury by MTV could be alleviated by anti-WISP1 antibody treatment. MTV further increased poly(I:C)-induced integrin β3 expression in the lung. We performed coimmunoprecipitation, which showed there was an interaction between WISP1 and β3. WISP1 significantly increased poly(I:C)-induced TNF-α production in macrophages isolated from WT mice, but not in macrophages isolated from β3 knockout mice. Cotreatment with WISP1 and poly(I:C) markedly increased the phosphorylation of extracellular signal-related kinase (ERK) in macrophages. Pretreating macrophages with an ERK inhibitor, U0126, dose-dependently antagonized the synergistic effect of WISP1 on poly(I:C)-induced TNF-α release. In conclusion, MTV exaggerates poly(I:C)-induced lung injury in a WISP1-and integrin β3-dependent manner, involving, at least in part, the activation of the ERK pathway. The WISP1-integrin β3 pathway could be a novel therapeutic target.

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“…The accumulation of neutrophils in the lung tissue can also lead to enhanced levels of inflammatory cytokines, which play fundamental roles in the development of lung pathogenesis, including VILI (9,10). Recent expression profiling using injurious and noninjurious MV in the presence and absence of inflammatory stimuli revealed the involvement of a complex network of genes encoding for matrix remodeling proteins, proinflammatory cytokines, and various transcription factors in VILI (11)(12)(13)(14)(15). The exact molecular mechanisms controlling the expression levels of these genes in response to MV and their contribution to the development or susceptibility to VILI are unclear.…”

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confidence: 99%

Genetic and Pharmacologic Evidence Links Oxidative Stress to Ventilator-induced Lung Injury in Mice

Papaiahgari

Yerrapureddy

Reddy

et al. 2007

Am J Respir Crit Care Med

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Rationale: Mechanical ventilation (MV) is an indispensable therapy for critically ill patients with acute lung injury and the adult respiratory distress syndrome. However, the mechanisms by which conventional MV induces lung injury remain unclear. Objectives: We hypothesized that disruption of the gene encoding Nrf2, a transcription factor that regulates the induction of several antioxidant enzymes, enhances susceptibility to ventilator-induced lung injury (VILI) and that antioxidant supplementation attenuates this effect. Methods: To test our hypothesis and to examine the relevance of oxidative stress in VILI, we assessed lung injury and inflammatory responses in Nrf2-deficient (Nrf2 2/2 ) mice and wild-type (Nrf2 1/1 ) mice after an acute (2-h) injurious model of MV with or without administration of antioxidant. Measurements and Main Results: Nrf2 2/2 mice displayed greater levels of lung alveolar and vascular permeability and inflammatory responses to MV as compared with Nrf2 1/1 mice. Nrf2 deficiency enhances the levels of several proinflammatory cytokines implicated in the pathogenesis of VILI. We found diminished levels of critical antioxidant enzymes and redox imbalance by MV in the lungs of Nrf2 2/2 mice; however, antioxidant supplementation to Nrf2 2/2 mice remarkably attenuated VILI. When subjected to a clinically relevant prolong period of MV, Nrf2 2/2 mice displayed greater levels of VILI than Nrf2 1/1 mice. Expression profiling revealed lack of induction of several VILI genes, stress response and solute carrier proteins, and phosphatases in Nrf2 2/2 mice. Conclusions: Our data demonstrate for the first time a critical role for Nrf2 in VILI, which confers protection against cellular responses induced by MV by modulating oxidative stress.

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Modulation of Lipopolysaccharide-Induced Gene Transcription and Promotion of Lung Injury by Mechanical Ventilation

Cited by 138 publications

References 40 publications

Fas (CD95) induces macrophage proinflammatory chemokine production via a MyD88-dependent, caspase-independent pathway

Fas (CD95) induces macrophage proinflammatory chemokine production via a MyD88-dependent, caspase-independent pathway

Mechanical Ventilation Augments Poly(I:C)-Induced Lung Injury via a WISP1-Integrin β3-Dependent Pathway in Mice

Genetic and Pharmacologic Evidence Links Oxidative Stress to Ventilator-induced Lung Injury in Mice

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