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(Journal of Leukocyte Biology. 2002;71:829-836.)
© 2002 by Society for Leukocyte Biology

Endothelins regulate mediator production of rat tissue-cultured mucosal mast cells. Up-regulation of Th1 and inhibition of Th2 cytokines

Martin Coulombe*, Bruno Battistini*, Jana Stankova{dagger}, Philippe Pouliot* and Elyse Y. Bissonnette*

* Centre de Recherche, Hôpital Laval, Institut Universitaire de Cardiologie et de Pneumologie, Université Laval, Québec, Canada; and
{dagger} Immunology Division, Université de Sherbrooke, Quebec, Canada

Correspondence: Dr. Elyse Bissonnette, Hôpital Laval, 2725, Chemin Sainte-Foy, Sainte-Foy, Quebec, Canada G1V 4G5. E-mail: elyse.bissonnette{at}med.ulaval.ca

Mast cells have been shown to produce endothelin-1 (ET-1) and to express ET receptors. Thus, we postulated that ETs modulate mast cell mediator production in an autocrine manner. Rat tissue-cultured mast cells (RCMC-1) were incubated with exogenous ET-1 or ET-3, and ß-hexosaminidase release and TNF, IL-4, IL-10, IL-12, IL-13, macrophage inflammatory protein-1{alpha} (MIP-1{alpha}), and nitric oxide (NO) production were investigated. ET-1 and -3 induced the release of ß-hexosaminidase and TNF and of mRNA expression. An antagonist of the ETB receptor subtype abrogated ET-stimulated TNF release, although ETA and ETB receptors have been identified by immunocytochemistry. It is interesting that ET-1 and ET-3 inhibited (25–30%) mRNA expression of Th2-type cytokines (IL-4, IL-10, and IL-13) and increased IL-12 release (39% and 41%, respectively) without affecting MIP-1{alpha} and NO production. Thus, our data suggest that ETs may play an important role in modulating the cytokine network by regulating Th1/Th2 cytokine production by mast cells.

Key Words: ET receptors • nitric oxide • TNF • ß-hexosaminidase • interleukin • macrophage inflammatory protein-1{alpha}




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