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Transient expression of prostaglandin endoperoxide synthase‐2 during mouse macrophage activation
Author(s) -
Riese Jutta,
Hoff Torsten,
Nordhoff Axel,
DeWitt David L.,
Resch Klaus,
Kaever Volkhard
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.55.4.476
Subject(s) - biology , lipopolysaccharide , nitric oxide synthase , macrophage , microbiology and biotechnology , gene isoform , prostaglandin , prostaglandin e2 , messenger rna , nitric oxide , tumor necrosis factor alpha , in vitro , endocrinology , biochemistry , gene
We investigated regulation of macrophage prostaglandin production during activation by interferonγ (IFN‐γ) and lipopolysaccharide (LPS). An in vitro model was established using the mouse macrophagelike cell line RAW 264.7. Cells were cultivated in the presence of IFN‐γ and LPS for up to 48 h and changes in the secretion of nitric oxide (NO) and tumor necrosis factor α (TNF‐ α ) were observed as activation markers. Under these conditions a prompt and strong increase in PGE 2 production was found in the first 8 h followed by nearly constant generation of PGE 2 during the next 40 h. In contrast, the activity of prostaglandin endoperoxide synthase (PGHS), measured as PGE 2 production of microsomal protein fractions, was also increased, but reached a clear maximum at 24 h. Recently a second form of PGHS was cloned (PGHS‐2) and specific antibodies and mRNA probes for both isoforms are available. PGHS‐2 enzyme was expressed maximally after 24 h of activation whereas PGHS‐1 was not influenced. In the presence of IFN‐γ and LPS, PGHS‐2 mRNA expression reached a maximum at 8 h but PGHS‐1 mRNA was not induced during the whole time period. These data indicate that changes in PG synthesis following macrophage activation are due to regulation of PGHS‐2 expression. J. Leukoc. Biol. 55: 476–482; 1994.