Signaling pathways in interleukin-1beta-mediated middle ear mucin secretion.

Abstract

The objectives of this study were to investigate the role of the phosphatidylcholine-specific phospholipase C (PC-PLC), protein kinase C (PKC), and nitric oxide synthase (NOS) pathways during upregulation of mucin secretion by middle ear epithelium after exposure to interleukin-1beta and to examine the ability of a specific interleukin-1 receptor antagonist (IL-1betara) to block this increased secretion. Primary chinchilla middle ear epithelial cultures were established and exposed to IL-1beta. Specific inhibitors of calmodulin, PC-PLC, PKC, and NOS pathways were used to investigate the potential role of these pathways leading to increased epithelial mucin secretion after exposure to IL-1beta. Mucin secretion was characterized by exclusion chromatography and liquid scintillation. Epithelial cultures exposed to IL-1beta demonstrate an increase in mucin secretion that is blocked by specific inhibitors of PC-PLC, PKC, and NOS, but not by inhibitors of calmodulin. In addition, mucin secretion stimulated by IL-1beta was reversible with use of a specific IL-1betara. IL-1beta stimulates mucin secretion from middle ear epithelium and its effects can be reversed by IL-1betara. PC-PLC, PKC, and NOS pathways play a role in the increased secretion of mucin in middle ear epithelial cells after exposure to IL-1beta.