Premium
Endothelins regulate mediator production of rat tissue‐cultured mucosal mast cells. Up‐regulation of Th1 and inhibition of Th2 cytokines
Author(s) -
Coulombe Martin,
Battistini Bruno,
Stankova Jana,
Pouliot Philippe,
Bissonnette Elyse Y.
Publication year - 2002
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.71.5.829
Subject(s) - biology , autocrine signalling , cytokine , mast cell , receptor , tumor necrosis factor alpha , mediator , histamine , endothelins , microbiology and biotechnology , receptor antagonist , endocrinology , medicine , immunology , endothelin receptor , antagonist , biochemistry
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 β‐hexosaminidase release and TNF, IL‐4, IL‐10, IL‐12, IL‐13, macrophage inflammatory protein‐1α (MIP‐1α), and nitric oxide (NO) production were investigated. ET‐1 and ‐3 induced the release of β‐hexosaminidase and TNF and of mRNA expression. An antagonist of the ET B receptor subtype abrogated ET‐stimulated TNF release, although ET A and ET B 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‐1α 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.