Peroxisome proliferator-activated receptor-γ inhibits cigarette smoke solution-induced mucin production in human airway epithelial (NCI-H292) cells

Lee, Sung Yong; Kang, Eun Joo; Hur, Gyu Young; Jung, Ki Hwan; Jung, Haeil; Lee, Sang Yeub; Kim, Je Hyeong; Shin, Chol; In, Kwang Ho; Kang, Kyung Ho; Yoo, Se Hwa; Shim, Jae Jeong

doi:10.1152/ajplung.00388.2005

Cited by 53 publications

(48 citation statements)

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“…Both the thiazolidinedione pioglitazone (29) and the endogenous PPAR␥ agonist 15-deoxy-⌬ 12,14 -prostaglandin J 2 (15d-PGJ 2 ) (30) have proven effective in the LPS-induced model of COPD, while both Rosi and pioglitazone were effective in a smoke-induced model (28). In vitro, Lee et al (31) attributed the ability of Rosi to inhibit CSE-induced TNF-␣ and mucin production in H292 cells to up-regulation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN), with consequent down-regulation of the Akt signaling pathway. However, Rosi did not block CSE-induced cytokine production in a monocyte-macrophage cell line in which CSE disrupts the association between PPAR␥ and NF-B (32).…”

Section: Discussionmentioning

confidence: 99%

Down-regulated Peroxisome Proliferator-activated Receptor γ (PPARγ) in Lung Epithelial Cells Promotes a PPARγ Agonist-reversible Proinflammatory Phenotype in Chronic Obstructive Pulmonary Disease (COPD)

Lakshmi

Reddy

Zhang

et al. 2014

Journal of Biological Chemistry

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Background:The mechanistic role of peroxisome proliferator-activated receptor ␥ (PPAR␥) in chronic obstructive pulmonary disease (COPD) is poorly understood. Results: COPD and cigarette smoke exposure down-regulated PPAR␥ and produced inflammation that PPAR␥ agonists reversed through multiple pathways. Conclusion: PPAR␥ plays a pivotal role in COPD. Significance: PPAR␥ agonists may be the first effective treatment for COPD.

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Section: Discussionmentioning

confidence: 99%

Down-regulated Peroxisome Proliferator-activated Receptor γ (PPARγ) in Lung Epithelial Cells Promotes a PPARγ Agonist-reversible Proinflammatory Phenotype in Chronic Obstructive Pulmonary Disease (COPD)

Lakshmi

Reddy

Zhang

et al. 2014

Journal of Biological Chemistry

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“…Specifically, PPARγ can modulate eosinophil survival and activation [47], as well as epithelial mucin production [48]. It is possible that the relatively rapid effects of γT against allergen-induced inflammation could be mediated by an acute activation of PPARγ to inhibit signaling cascades that lead to airway inflammatory cell recruitment and activation.…”

Section: Discussionmentioning

confidence: 99%

Ozone enhancement of lower airway allergic inflammation is prevented by γ-tocopherol

Wagner

Jiang

Harkema

et al. 2007

Free Radical Biology and Medicine

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Ozone is a commonly encountered environmental oxidant which has been linked to asthma exacerbation in epidemiological studies. Ozone induces airway inflammation and enhances response to inhaled allergen. It has been suggested that antioxidant therapy may minimize the adverse effects of ozone in asthma. We have previously shown that the antioxidant gammatocopherol (γT), an isoform of vitamin E, also has anti-inflammatory effects. We employed a Brown Norway rat model of ozone-enhanced allergic responses to test the therapeutic effects of γT on O 3 -induced airway inflammation. Ovalbumin (OVA) -sensitized rats were intranasally challenged with 0 or 0.5% OVA on Days 1 and 2, and exposed to 0 or 1 ppm ozone (8h/day) on Days 4 and 5. Rats were also given 0 or 100 mg/kg γT on Days 2 through 5. Pulmonary tissue and bronchoalveolar lavage fluid (BALF) were collected on Day 6. OVA challenge caused increased total cells (267% increase) and eosinophils (4000%) in BALF that was unaffected by ozone exposure. Morphometric evaluation of lung tissue revealed increases in intraepithelial mucosubstances (IM) (300%) and subepithelial eosinophils (400%) in main axial airways. Ozone exposure of allergic rats enhanced IM increases in proximal axial airways (200%), induced cysleukotrienes, MCP-1 and IL-6 production in BALF, and upregulated expression of IL-5 and IL-13 mRNA. γT treatment had no effect on IM increases by allergen, but blocked enhancement by ozone. γT attenuated both OVA-or ozone -stimulated eosinophilic infiltration, and increases of BALF cys-leukotrienes, MCP-1 and IL-6, as well as IL-5 and IL-13 mRNA. These data Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. HHS Public Access Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript demonstrate broad anti-inflammatory effects of a γT and suggest it may be an effective therapy of allergic airway inflammation.

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“…EGF and eosinophilderived TGF-, another natural ligand for the EGFR, have been shown to stimulate MUC5AC mucin gene expression and protein synthesis in a human airway epithelial cell line, and goblet cell metaplasia (Burgel and Nadel, 2004). The expression and activation of EGFR causes goblet cell metaplasia from Clara cells by a process of cell differentiation Nadel, 2001;Nadel and Burgel, 2001;Lee et al, 2006b). These goblet cell metaplasia and increased mucin production are important factors contributing to disease pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

Potential use of an anticancer drug gefinitib, an EGFR inhibitor, on allergic airway inflammation

Hur

Lee²,

Lee³

et al. 2007

Exp Mol Med

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The EGFR plays an essential role in goblet cell hyperplasia and mucus hypersecretion. EGFR has an intrinsic tyrosine kinase activity that, when activated, induces the production of MUC5AC through the signaling kinase cascade in the airway epithelium. We have investigated the effects of an EGFR tyrosine kinase inhibitor, gefitinib, on ovalbumin (OVA)-induced, allergic inflammation in airway epithelia of mice. OVA-sensitized mice were pretreated with gefitinib at two different doses (12.5 and 50 mg/kg) and then challenged with OVA. The OVA challenge increased the total cell count and eosinophil count in bronchoalveolar lavage fluid (BALF), as well as the concentrations of T-helper2 (Th2) cytokines, such as IL-4 and IL-13, overall eosinophil recruitment in the lung tissue and airway hyperresponsiveness (AHR). Pretreatment with gefitinib reduced the inflammatory cell counts and released cytokine concentrations (IL-4 and IL-13) in BALF, as well as eosinophil recruitment in the lungs and AHR, in a dose-dependent manner. This was associated with decreased EGFR and Akt phosphorylation. We showed that gefitnib inhibits EGFR and phosphoinositol 3'-kinase (PI3K)/Akt activation which were activated in OVA sensitized mice. These findings suggest that inhibitors of the EGFR cascade may have a role in the treatment of asthma.

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Peroxisome proliferator-activated receptor-γ inhibits cigarette smoke solution-induced mucin production in human airway epithelial (NCI-H292) cells

Cited by 53 publications

References 54 publications

Down-regulated Peroxisome Proliferator-activated Receptor γ (PPARγ) in Lung Epithelial Cells Promotes a PPARγ Agonist-reversible Proinflammatory Phenotype in Chronic Obstructive Pulmonary Disease (COPD)

Down-regulated Peroxisome Proliferator-activated Receptor γ (PPARγ) in Lung Epithelial Cells Promotes a PPARγ Agonist-reversible Proinflammatory Phenotype in Chronic Obstructive Pulmonary Disease (COPD)

Ozone enhancement of lower airway allergic inflammation is prevented by γ-tocopherol

Potential use of an anticancer drug gefinitib, an EGFR inhibitor, on allergic airway inflammation

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