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TGF‐beta 1 inhibits both endotoxin‐induced prostaglandin synthesis and expression of the TIS10/prostaglandin synthase 2 gene in murine macrophages
Author(s) -
Reddy Srinivasa T.,
Gilbert Rebecca S.,
Xie Weilin,
Luner Steven,
Herschman Harvey R.
Publication year - 1994
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 - 10.1002/jlb.55.2.192
Subject(s) - cytokine , lipopolysaccharide , biology , nitric oxide , paracrine signalling , prostaglandin , macrophage , nitric oxide synthase , prostaglandin e2 , transforming growth factor beta , cell culture , tgf beta 1 , endocrinology , medicine , transforming growth factor , microbiology and biotechnology , biochemistry , immunology , in vitro , receptor , genetics
Activated macrophages produce substantial quantities of paracrine mediators, including cytokines, nitric oxide, and prostaglandins. Transforming growth factor beta 1 (TGF‐beta) is a potent modulator of immune function. TGF‐beta inhibits the cytotoxic activity of en‐dotoxin/lipopolysaccharide (LPS)‐activated macrophage cell lines and primary macrophage cultures, reducing their expression of cytokines and nitric oxide. In this report we demonstrate that TGF‐beta also attenuates the LPS‐induced synthesis and secretion of prostaglandin E 2 in murine RAW 264.7 macrophage cells. Macrophage activation also induces accumulation of the recently described ligand‐responsive prostaglandin synthase (PGS) TIS10/PGS‐2. While TGF‐beta alone has no effect on expression from the TIS10/PGS‐2 gene, this cytokine inhibits LPS‐induced TIS10/PGS‐2 protein accumulation and synthesis, as well as LPS‐induced TIS10/PGS‐2 message accumulation in RAW 264.7 cells. TGF‐beta concentrations in the range of 0.1–1.0 ng/ml (4–40 pM) maximally inhibit LPS‐induced TIS10/PGS‐2 message accumulation. In contrast, neither LPS nor TGF‐beta has any effect on the level of PGS‐1 (EG 1.14.99.1) message. TGF‐beta also attenuates LPS‐induced accumulation of unspliced TIS10/PGS‐2 transcripts in RAW 264.7 cells, suggesting that this cytokine exerts its effects on TIS10/PGS‐2 expression at the transcriptional level. TGF‐beta inhibits the LPS‐induced accumulation of TIS10/PGS‐2 protein and message in cultured murine peritoneal macrophages, as well as in macrophage cell lines. J. Leukoc. Biol. 55: 192–200; 1994.