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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Division of Pediatric Otolaryngology and the Department of Otolaryngology and Communication Sciences, Medical College of Wisconsin, Milwaukee, WI 53226, USA. kersch@mcw.edu
Joseph E
JE
Kerschner
Chris
C
Yang
Amy
A
Burrows
Joseph A
JA
Cioffi
D000818:Animals; D002147:Calmodulin / Q000037:antagonists & inhibitors / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002682:Chinchilla; D004432:Ear, Middle / Q000187:drug effects / Q000378:metabolism*; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009077:Mucins / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000502:physiology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D015398:Signal Transduction; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000502:physiology; D015854:Up-Regulation
D002147:Calmodulin; D007375:Interleukin-1; D009077:Mucins; D017472:Receptors, Interleukin-1; D019001:Nitric Oxide Synthase; D011493:Protein Kinase C; D010738:Type C Phospholipases; C105598:phosphatidylcholine-specific phospholipase C