title: Peroxisome proliferator-activated receptor-gamma inhibits cigarette smoke solution-induced mucin production in human airway epithelial (NCI-H292) cells.
abstract: The main etiologic factor for chronic bronchitis is cigarette smoke. Exposure to cigarette smoke is reported to induce goblet cell hyperplasia and mucus production. Mucin synthesis in airways has been reported to be regulated by the EGFR system. Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a member of the ligand-activated nuclear receptor superfamily. PPAR-gamma is implicated in anti-inflammatory responses, but mechanisms underlying these varied roles remain ill-defined. Recently, reports have shown that upregulation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) might be one of the mechanisms through which PPAR-gamma agonists exert their anti-inflammatory actions. However, no data are available on the role of PPAR-gamma in smoke-induced mucin production. In this study, we investigated the effect of PPAR-gamma agonist (rosiglitazone) on smoke-induced mucin production in NCI-H292 cells. Exposure to cigarette smoke causes a significant decrease in PTEN expression and increases dose-dependent EGFR-specific tyrosine phosphorylation, resulting in MUC5AC mucin production in NCI-H292 cells. PPAR-gamma agonists or specific inhibitors of phosphoinositide 3-kinase exert inhibition of cigarette smoke-induced mucin production, with the upregulation of PTEN signaling and downregulation of Akt expression. This study demonstrates that PPAR-gamma agonist functions as a regulator of epithelial cell inflammation that may result in reduction of mucin-producing cells in airway epithelium.
authors.affiliation: Dept. of Internal Medicine, Korea Univ. Guro Hospital, #80, Guro-dong, Guro-gu, Seoul, Republic of Korea.
authors.forename: Sung Yong
authors.initials: SY
authors.lastname: Lee
authors.forename: Eun Joo
authors.initials: EJ
authors.lastname: Kang
authors.forename: Gyu Young
authors.initials: GY
authors.lastname: Hur
authors.forename: Ki Hwan
authors.initials: KH
authors.lastname: Jung
authors.forename: Hye Cheol
authors.initials: HC
authors.lastname: Jung
authors.forename: Sang Yeub
authors.initials: SY
authors.lastname: Lee
authors.forename: Je Hyeong
authors.initials: JH
authors.lastname: Kim
authors.forename: Chol
authors.initials: C
authors.lastname: Shin
authors.forename: Kwang Ho
authors.initials: KH
authors.lastname: In
authors.forename: Kyung Ho
authors.initials: KH
authors.lastname: Kang
authors.forename: Se Hwa
authors.initials: SH
authors.lastname: Yoo
authors.forename: Jae Jeong
authors.initials: JJ
authors.lastname: Shim
mesh_terms: D018277:Carcinoma, Mucoepidermoid; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008175:Lung Neoplasms; D055271:Mucin 5AC; D009077:Mucins / Q000378:metabolism*; D047495:PPAR gamma / Q000819:agonists / Q000378:metabolism*; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011799:Quinazolines; D020545:Respiratory Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000077154:Rosiglitazone; D012907:Smoking / Q000009:adverse effects*; D045162:Thiazolidinediones / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism; D020032:Tyrphostins / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D066246:ErbB Receptors; D007004:Hypoglycemic Agents; D055271:Mucin 5AC; D009077:Mucins; D047495:PPAR gamma; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D011799:Quinazolines; D000077154:Rosiglitazone; D045162:Thiazolidinediones; D014409:Tumor Necrosis Factor-alpha; D014443:Tyrosine; D020032:Tyrphostins; C524678:MUC5AC protein, human; C101044:RTKI cpd; C494929:PTEN protein, human