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 ant itumoral activity, is now recognized as a polypeptide mediator of infl ammatory and cellular immune response. Recent studies have demonstrate d 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 glyc oprotein (MGP) secretion from cultured chinchilla middle ear epithelia l cells were examined, and TNF-alpha was found to stimulate MGP secret ion in a time- and concentration-dependent manner. The action of TNF-a lpha on MGP secretion was significantly and dose-dependently inhibited by TNF-alpha monoclonal antibody; this finding is suggestive of its s pecificity on MGP secretion. The addition of the protein kinase C inhi bitor 1-(5-isoquinolinylsulfonyl)-2-methylpiperidine (H-7) to the cult ure significantly blocked TNF-alpha-induced MGP secretion, while the c almodulin 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.