Endothelins regulate mediator production of rat tissue-cultured mucosal mast cells. Up-regulation of Th1 and inhibition of Th2 cytokines.
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 beta-hexosaminidase release and TNF, IL-4, IL-10, IL-12, IL-13, macrophage inflammatory protein-1alpha (MIP-1alpha), and nitric oxide (NO) production were investigated. ET-1 and -3 induced the release of beta-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-1alpha 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.
Coulombe
Martin
M
Centre de Recherche, Hôpital Laval, Institut Universitaire de Cardiologie et de Pneumologie, Université Laval, 2725 Chemin Sainte-Foy, Sainte-Foy, Québec, Canada G1V 4G5.
Battistini
Bruno
B
Stankova
Jana
J
Pouliot
Philippe
P
Bissonnette
Elyse Y
EY
D000818:Animals; D002460:Cell Line; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D046508:Culture Techniques; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D019332:Endothelin-1 / Q000494:pharmacology*; D019334:Endothelin-3 / Q000494:pharmacology*; D005786:Gene Expression Regulation; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology*; D009092:Mucous Membrane / Q000166:cytology; D009569:Nitric Oxide / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017466:Receptors, Endothelin / Q000502:physiology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014158:Transcription, Genetic / Q000187:drug effects; D015854:Up-Regulation; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism
D054405:Chemokine CCL3; D054407:Chemokine CCL4; D016207:Cytokines; D019332:Endothelin-1; D019334:Endothelin-3; D019402:Macrophage Inflammatory Proteins; D012333:RNA, Messenger; D017466:Receptors, Endothelin; D009569:Nitric Oxide; D001619:beta-N-Acetylhexosaminidases