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Effects of IL‐1β, TNF‐α, and macrophage migration inhibitory factor on prostacyclin synthesis in rat pulmonary artery smooth muscle cells
Author(s) -
ITOH Akihide,
NISHIHIRA Jun,
MAKITA Hironi,
MIYAMOTO Kenji,
YAMAGUCHI Etsuro,
NISHIMURA Masaharu
Publication year - 2003
Publication title -
respirology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 85
eISSN - 1440-1843
pISSN - 1323-7799
DOI - 10.1046/j.1440-1843.2003.00491.x
Subject(s) - prostacyclin , macrophage migration inhibitory factor , medicine , tumor necrosis factor alpha , cyclooxygenase , endocrinology , arachidonic acid , pulmonary artery , proinflammatory cytokine , cytokine , pulmonary hypertension , inflammation , pharmacology , biology , enzyme , biochemistry
Objective: Cytokines have been implicated in the pathophysiology of pulmonary hypertension. We sought to explore the possibility that prostacyclin is a link. Methodology: We tested the effects of the cytokines interleukin‐1β (IL‐1β), tumour necrosis factor‐α (TNF‐α), and macrophage migration inhibitory factor (MIF) on arachidonic acid metabolism of pulmonary artery smooth muscle cells (PASMCs) with special regard to prostacyclin (PGI 2 ) that protects against pulmonary hypertension. Cultured rat PASMCs were treated with IL‐1β, TNF‐α, or MIF. Expression of prostacyclin synthase (PGIS) and cyclooxygenase‐2 (COX‐2) mRNAs, and PGI 2 synthesis, were measured. Results: We found that PGIS mRNA expression was suppressed by high concentrations of TNF‐α and MIF, while COX‐2 mRNA was induced by all three cytokines tested. IL‐1β increased PGI 2 production in a dose‐dependent manner. TNF‐α and MIF also increased PGI 2 production, but to a far lesser degree at high concentrations. TNF‐α paradoxically decreased PGI 2 production at a low concentration. Conclusions: These results suggest that TNF‐α and MIF are potentially antagonistic to the action of PGI 2 in rat PASMCs via down‐regulation of PGIS mRNA. Simultaneous induction of COX‐2 mRNA may further counteract the action of PGI 2 by increasing the levels of eicosanoids other than PGI 2 .