title: Effect of thymic stromal lymphopoietin on MUC5B expression in human airway epithelial cells.
abstract: Thymic stromal lymphopoietin (TSLP) is an interleukin 7-like cytokine and a potent factor for B- and T-cell growth and differentiation. Recent studies have demonstrated an association of TSLP with allergic and inflammatory airway diseases. However, no study on the effect of TSLP on expression of mucin genes in airway epithelial cells has been reported. Therefore, the effects and brief signaling pathways of TSLP on expression of mucin genes in human airway epithelial cells were investigated in this study. In mucin-producing human NCI-H292 airway epithelial cells and primary cultures of normal nasal epithelial cells, the effect and signaling pathway of TSLP on expression of mucin genes were investigated using reverse transcriptase-polymerase chain reaction (RT-PCR), real-time PCR, enzyme immunoassay, and immunoblot analysis with several specific inhibitors and small interfering RNA (siRNA). In human NCI-H292 airway epithelial cells, TSLP increased MUC5B expression. TSLP significantly activated phosphorylation of ERK1/2 and p38 mitogen-activated protein kinase (MAPK). U0126 (ERK1/2 MAPK inhibitor) and SB203580 (p38 MAPK inhibitor) significantly attenuated TSLP-induced MUC5B mRNA expression. Knockdown of ERK1, ERK2, and p38 MAPK by ERK1, ERK2, and p38 MAPK siRNA significantly blocked TSLP-induced MUC5B mRNA expression. In the primary cultures of normal nasal epithelial cells, TSLP significantly increased MUC5B mRNA expression, which was significantly attenuated after pretreatment with U0126 and SB203580. These results suggest that TSLP induces MUC5B expression via the ERK1/2 and p38 MAPK signaling pathway in human airway epithelial cells.
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Yeungnam University, Daegu, Republic of Korea.
authors.forename: Chang Hoon
authors.initials: CH
authors.lastname: Bae
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Yeungnam University, Daegu, Republic of Korea.
authors.forename: Yoon Seok
authors.initials: YS
authors.lastname: Choi
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Yeungnam University, Daegu, Republic of Korea.
authors.forename: Si-Youn
authors.initials: SY
authors.lastname: Song
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Yeungnam University, Daegu, Republic of Korea; Regional Center for Respiratory Diseases, Yeungnam University Medical Center, Daegu, Republic of Korea. Electronic address: ydkim@med.yu.ac.kr.
authors.forename: Yong-Dae
authors.initials: YD
authors.lastname: Kim
mesh_terms: D002070:Butadienes / Q000494:pharmacology; D018394:CA-125 Antigen / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000235:genetics; D055271:Mucin 5AC / Q000235:genetics / Q000378:metabolism; D055264:Mucin-4 / Q000235:genetics / Q000378:metabolism; D055257:Mucin-5B / Q000235:genetics / Q000378:metabolism*; D009297:Nasal Mucosa / Q000166:cytology* / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D010766:Phosphorylation; D011725:Pyridines / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D002070:Butadienes; D018394:CA-125 Antigen; D016207:Cytokines; D007093:Imidazoles; C451759:MUC16 protein, human; C524658:MUC4 protein, human; C524678:MUC5AC protein, human; C524578:MUC5B protein, human; D008565:Membrane Proteins; D055271:Mucin 5AC; D055264:Mucin-4; D055257:Mucin-5B; D009570:Nitriles; D011725:Pyridines; C113580:U 0126; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580; D000094632:Thymic Stromal Lymphopoietin
keywords: Airway epithelial cell; ERK1/2; MUC5B; Thymic stromal lymphopoietin; p38