Mechanisms of mucin production by rhinovirus infection in cultured human airway epithelial cells.
Mucus hypersecretion relates to exacerbations of bronchial asthma and chronic obstructive pulmonary disease (COPD) caused by rhinovirus (RV) infection. We examined the mechanisms of RV infection-induced mucin production in human tracheal surface epithelial cells and submucosal gland cells. RV14 up-regulated the mRNA expression of MUC2, MUC3, MUC5AC, MUC5B and MUC6, and increased MUC5AC and total mucin concentration in supernatants and lysates of the surface cells. An inhibitor of the nuclear factor kappaB caffeic acid phenylethyl ester, inhibitors of selective p44/42 mitogen-activated protein kinase-kinase PD98059 and U0126, and a selective Src inhibitor PP1 attenuated MUC5AC mRNA expression, and secretion and production of MUC5AC and total mucin glycoprotein in the surface cells. In the gland cells, RV14 also increased mRNA expression of MUC2, MUC5AC, MUC5B and MUC7, and the inhibitors attenuated the secretion of total mucin glycoprotein. Src-related p44/42 mitogen-activated protein kinase pathway may be associated with RV-induced mucin hypersecretion in human airways.
Inoue
Daisuke
D
Department of Geriatric and Respiratory Medicine, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.
Yamaya
Mutsuo
M
Kubo
Hiroshi
H
Sasaki
Takahiko
T
Hosoda
Masayoshi
M
Numasaki
Muneo
M
Tomioka
Yoshihisa
Y
Yasuda
Hiroyasu
H
Sekizawa
Kiyohisa
K
Nishimura
Hidekazu
H
Sasaki
Hidetada
H
D000368:Aged; D000906:Antibodies / Q000494:pharmacology; D002102:Cadaver; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology; D004622:Embryo, Mammalian; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology; D042541:Intracellular Space / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D055271:Mucin 5AC; D009077:Mucins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D010850:Picornaviridae Infections / Q000378:metabolism* / Q000821:virology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D020545:Respiratory Mucosa / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D012229:Rhinovirus / Q000302:isolation & purification; D015398:Signal Transduction; D014132:Trachea / Q000187:drug effects / Q000378:metabolism* / Q000821:virology; D019562:Viral Load
D000906:Antibodies; D016207:Cytokines; C524678:MUC5AC protein, human; D055271:Mucin 5AC; D009077:Mucins; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1