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Timing of prostaglandin exposure is critical for the inhibition of LPS‐ or IFN‐γ‐induced macrophage NO synthesis by PGE 2
Author(s) -
Harbrecht B. G.,
Kim YM.,
Wirant E. A.,
Simmons R. L.,
Billiar T. R.
Publication year - 1997
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.61.6.712
Subject(s) - biology , macrophage , prostaglandin e2 , prostaglandin , immunology , pharmacology , microbiology and biotechnology , medicine , endocrinology , biochemistry , in vitro
Macrophage nitric oxide (NO) synthesis is an integral component of the host defense system. We have previously found that NO and prostaglandins interact in a variety of ways. NO modulates Kupffer cell prostaglandin E 2 (PGE 2 ) production and we have recently described the inhibitory effects of PGE 2 on NO synthesis in both Kupffer cells and hepatocytes. Activated macrophages produce a number of prostaglandins but studies regarding the capacity of prostaglandins to regulate macrophage NO synthesis have yielded conflicting results. We found that exogenous PGE 2 decreased lipopolysaccharide (LPS)‐induced NO synthesis in murine resident peritoneal macrophages and in the RAW 264.7 murine macrophage cell line. PGE 2 also suppressed NO synthesis in response to interferon‐γ (IFN‐γ) alone and a combination of LPS + IFN‐γ. Inhibition of endogenous PGE 2 synthesis with indomethacin or ibuprofen had no effect on NO synthesis. PGE 2 added with the activating stimulus was most effective. PGE 2 lost the capacity to block NO synthesis if added more than 180 min after LPS. PGE 2 decreased inducible NO synthase (iNOS) mRNA and immunoreactive iNOS protein, consistent with the hypothesis that exogenous PGE 2 inhibits macrophage iNOS expression but that the inhibition depends on the time and concentration of prostaglandin exposure. J. Leukoc. Biol . 61: 712–720; 1997.