Differential Role of the Fas/Fas Ligand Apoptotic Pathway in Inflammation and Lung Fibrosis Associated with Reovirus 1/L-Induced Bronchiolitis Obliterans Organizing Pneumonia and Acute Respiratory Distress Syndrome

Lopez, Andrea D; Avasarala, Sreedevi; Grewal, Suman; Murali, Anuradha K.; London, Lucille

doi:10.4049/jimmunol.0901958

Cited by 27 publications

(23 citation statements)

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“…Curcumin has also been shown to attenuate gefitinib-induced cell proliferation and enhances apoptosis through altering p38 MAPK activation in intestinal epithelia cell [85]. In the reovirus 1/L-ALI/ARDS model, we have clearly demonstrated a role for apoptosis in reovirus 1/L-ALI/ARDS [9]. Although we demonstrated both apoptosis of the alveolar epithelium via TUNEL analysis and the up regulation of Fas and FasL in situ in alveolar epithelium and in cells of the inflammatory infiltrate, modulation of reovirus 1/L-ALI/ARDS was not linked to the inhibition of the Fas/FasL pathway suggesting the involvement of additional apoptosis pathways [9].…”

Section: Discussionmentioning

confidence: 64%

“…As with ARDS in human patients, corticosteroids were ineffective in attenuating the infiltration of inflammatory leukocytes, suppressing key cytokine/chemokine expression, and inhibiting the development of fibrotic lesions in reovirus 1/L-ALI/ARDS [7], [8]. Finally, aberrant apoptosis has been proposed as one mechanism leading to fibrotic lesion development in ALI/ARDS, and we have demonstrated an indirect role for the Fas/FasL pathway in reovirus 1/L-ALI/ARDS [9]. Therefore, our model provides a very clinically relevant model for infection-induced acute viral pneumonia leading to ALI/ARDS.…”

Section: Introductionmentioning

confidence: 60%

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Curcumin Modulates the Inflammatory Response and Inhibits Subsequent Fibrosis in a Mouse Model of Viral-induced Acute Respiratory Distress Syndrome

et al. 2013

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Acute Respiratory Distress Syndrome (ARDS) is a clinical syndrome characterized by diffuse alveolar damage usually secondary to an intense host inflammatory response of the lung to a pulmonary or extrapulmonary infectious or non-infectious insult often leading to the development of intra-alveolar and interstitial fibrosis. Curcumin, the principal curcumoid of the popular Indian spice turmeric, has been demonstrated as an anti-oxidant and anti-inflammatory agent in a broad spectrum of diseases. Using our well-established model of reovirus 1/L-induced acute viral pneumonia, which displays many of the characteristics of the human ALI/ARDS, we evaluated the anti-inflammatory and anti-fibrotic effects of curcumin. Female CBA/J mice were treated with curcumin (50 mg/kg) 5 days prior to intranasal inoculation with 107 pfu reovirus 1/L and daily, thereafter. Mice were evaluated for key features associated with ALI/ARDS. Administration of curcumin significantly modulated inflammation and fibrosis, as revealed by histological and biochemical analysis. The expression of IL-6, IL-10, IFNγ, and MCP-1, key chemokines/cytokines implicated in the development of ALI/ARDS, from both the inflammatory infiltrate and whole lung tissue were modulated by curcumin potentially through a reduction in the phosphorylated form of NFκB p65. While the expression of TGFß1 was not modulated by curcumin, TGFß Receptor II, which is required for TGFß signaling, was significantly reduced. In addition, curcumin also significantly inhibited the expression of α-smooth muscle actin and Tenascin-C, key markers of myofibroblast activation. This data strongly supports a role for curcumin in modulating the pathogenesis of viral-induced ALI/ARDS in a pre-clinical model potentially manifested through the alteration of inflammation and myofibroblast differentiation.

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Section: Discussionmentioning

confidence: 64%

Section: Introductionmentioning

confidence: 60%

Curcumin Modulates the Inflammatory Response and Inhibits Subsequent Fibrosis in a Mouse Model of Viral-induced Acute Respiratory Distress Syndrome

et al. 2013

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“…Other representative genes involved in apoptosis, such as the Casp1, Casp2, Casp3, Casp4, Casp7, Casp8, and Casp12 genes, which encode members of the cysteine-aspartic acid protease (caspase) family, and the Tp53 gene (plays a critical role in cell cycle arrest, DNA repair, and apoptosis), were scarcely altered for all periods. It has been reported that apoptosis via the Fas/Fas ligand pathway plays an important role in the development of acute lung injury and fibrosis (Lopez et al, 2009). In this study, expression of Fas (TNF receptor superfamily, member 6) and Faslg (ligand that binds the Fas receptor; plays a role in induction of apoptosis) genes were unchanged over 6 months.…”

Section: Genbankmentioning

confidence: 84%

Identification of potential biomarkers from gene expression profiles in rat lungs intratracheally instilled with C60 fullerenes

et al. 2010

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“…Caspase-3, a key member of the caspase family, is widely accepted as a reliable indicator for cell apoptosis (15). Fas is an important molecule in the regulation of apoptosis (16). Bad is a pro-apoptotic protein in the Bcl-2 family (17).…”

Section: Resultsmentioning

confidence: 99%

Acid-induced cell injury and death in lung epithelial cells is associated with the activation of mitogen-activated protein kinases

Chen

Huang

Yang

et al. 2013

Molecular Medicine Reports

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Abstract. Gastric hydrochloric acid (HCl) has been regarded as a causative factor of acute lung injury (ALI). The activation of mitogen-activated protein kinases (MAPKs) has been suggested to be a mechanism involved in the pathogenesis of ALI in vivo. However, the effects of HCl on MAPK activation in lung epithelial cells remain to be fully elucidated. Further investigation into the role of MAPK activation in acid-induced cell injury and death is also needed. In the present study, BEAS-2B cells were treated with HCl (pH 4.0 medium) for 5, 15 and 30 min, and the acidified medium was then removed. Cell viability and death were detected by MTT assay and trypan blue exclusion staining, respectively. The activation of MAPKs [c-Jun N-terminal kinase (JNK), p38 MAPK and extracellular signal-regulated kinase (ERK) 1/2] was analyzed by western blot analysis. Cytotoxicity was assessed by lactate dehydrogenase (LDH) release, and IL-8 levels in culture supernatants were measured by enzyme-linked immunosorbent assay (ELISA). Cell apoptosis was detected as changes in the levels of capase-3, Bad and fas by western blot analysis and the number of apoptotic cells by using Annexin V/propidium iodide (PI) staining. Following pre-treatment with the JNK inhibitor II (10 µmol/l), the p38 inhibitor SB202190 (10 µmol/l) or the ERK inhibitor U0126 (10 µmol/l) for 30 min, BEAS-2B cells were exposed to HCl for 30 min. Cell viability, cytotoxicity, IL-8 levels and apoptosis were detected 4 h following acid stimulation. The viability of BEAS-2B cells was inhibited and cell death was increased in the presence of HCl. HCl stimulation induced activation of MAPKs in a time-dependent manner. HCl exposure increased the levels of IL-8 and the release of LDH, and induced apoptosis in BEAS-2B cells. JNK and p38 inhibitors increased cell viability and decreased cytotoxicity and cell apoptosis, while ERK inhibitor had no effect on cell viability, cytotoxicity or apoptosis. These results indicate that acid exposure induced epithelial cell injury and death. The activation of JNK and p38 is involved in HCl-induced epithelial lung cell injury and death. IntroductionAcute respiratory distress syndrome (ARDS) is a multifactorial, heterogeneous disease associated with high rates of mortality and disability in critically ill patients (1-3). Acid aspiration-induced lung injury accounts for ~11% of all clinical ARDS cases and is a major cause of morbidity in cases of critical illness (4,5). Acid aspiration-induced ARDS is characterized by pulmonary edema from increased vascular and epithelial permeability, as well as alveolar and interstitial inflammation with leukocyte infiltration (6). Cell death has been demonstrated in the lung during the pathogenesis of acute lung injury (ALI)/ARDS. However, the mechanism of acid-induced cell injury and death in ALI has yet to be fully elucidated.Mitogen-activated protein kinases (MAPKs), including the c-Jun NH2-terminal kinase (JNK), p38 MAPK and extracellular signal-regulated kinase (ERK) 1/2, are commonly involved in th...

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Differential Role of the Fas/Fas Ligand Apoptotic Pathway in Inflammation and Lung Fibrosis Associated with Reovirus 1/L-Induced Bronchiolitis Obliterans Organizing Pneumonia and Acute Respiratory Distress Syndrome

Cited by 27 publications

References 86 publications

Curcumin Modulates the Inflammatory Response and Inhibits Subsequent Fibrosis in a Mouse Model of Viral-induced Acute Respiratory Distress Syndrome

Curcumin Modulates the Inflammatory Response and Inhibits Subsequent Fibrosis in a Mouse Model of Viral-induced Acute Respiratory Distress Syndrome

Identification of potential biomarkers from gene expression profiles in rat lungs intratracheally instilled with C60 fullerenes

Acid-induced cell injury and death in lung epithelial cells is associated with the activation of mitogen-activated protein kinases

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