Increase of mucous glycoprotein secretion by tumor necrosis factor alpha via a protein kinase C-dependent mechanism in cultured chinchilla middle ear epithelial cells.
Tumor necrosis factor alpha (TNF-alpha), originally defined by its antitumoral activity, is now recognized as a polypeptide mediator of inflammatory and cellular immune response. Recent studies have demonstrated that TNF-(alpha exists in the fluid of otitis media with effusion and, therefore, suggested its possible role in the pathogenesis of mucus hypersecretion. In this study, the effects of TNF-alpha on mucous glycoprotein (MGP) secretion from cultured chinchilla middle ear epithelial cells were examined, and TNF-alpha was found to stimulate MGP secretion in a time- and concentration-dependent manner. The action of TNF-alpha on MGP secretion was significantly and dose-dependently inhibited by TNF-alpha monoclonal antibody; this finding is suggestive of its specificity on MGP secretion. The addition of the protein kinase C inhibitor 1-(5-isoquinolinylsulfonyl)-2-methylpiperidine (H-7) to the culture significantly blocked TNF-alpha-induced MGP secretion, while the calmodulin inhibitor N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) did not. This suggests that TNF-alpha stimulates MGP secretion via a protein kinase C-dependent mechanism.
Lin
J
J
University of Minnesota Otitis Media Research Center, Department of Otolaryngology, Minneapolis, USA.
Kim
Y
Y
Juhn
S K
SK
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000494:pharmacology; D000818:Animals; D000911:Antibodies, Monoclonal; D002478:Cells, Cultured; D002682:Chinchilla; D004305:Dose-Response Relationship, Drug; D004432:Ear, Middle / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004848:Epithelium / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism*; D010034:Otitis Media with Effusion / Q000503:physiopathology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D004791:Enzyme Inhibitors; D006023:Glycoproteins; D013449:Sulfonamides; D014409:Tumor Necrosis Factor-alpha; C047874:gastric mucus glycoproteins; C017967:W 7; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C