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Cytokine regulation of adult human osteoblast‐like cell prostaglandin biosynthesis
Author(s) -
Xu JiaQuan,
Cissel David S.,
Varghese Samuel,
Whipkey Diana L.,
Blaha J. David,
Graeber Geoffrey M.,
Keeting Philip E.
Publication year - 1997
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/(sici)1097-4644(19970315)64:4<618::aid-jcb10>3.0.co;2-8
Subject(s) - autocrine signalling , cytokine , metabolite , tumor necrosis factor alpha , prostaglandin e2 , biosynthesis , prostaglandin , prostacyclin , prostaglandin e , medicine , endocrinology , stimulation , antibody , chemistry , biology , biochemistry , immunology , receptor , enzyme
Prostaglandin (PG) biosynthesis by cytokine stimulated normal adult human osteoblast‐like (hOB) cells was evaluated by thin layer chromatography, high performance liquid chromatography, and specific immunoassays. PGE 2 was the predominant PG formed under all incubation conditions tested. Control samples produced measurable amounts of PGE 2 , and the measured level of this metabolite increased by 22‐fold (from 7 to 152 ng/ml) following a 20 h treatment with the combination of TGFβ and tumor necrosis factor‐α(TNF). The production of 6‐keto‐PGF 1α (the stable metabolite of prostacyclin) and of PGF 2α were each increased by about five‐fold (from about 0.5 to 2.5 ng/ml) in samples treated with the cytokines. Thus, TGFβ and TNF exerted a regulation of hOB cell PG biosynthesis that was principally directed towards an increased PGE 2 biosynthesis, with lesser effects on the production of other PG metabolites. COX‐2 mRNA levels were increased within 2 h of cytokine stimulation, reached a maximum at 6–12 h, and levels had appreciably diminished by 24 h after treatment. Both TGFβ and TNF could independently increase COX‐2 mRNA levels and PG biosynthesis. However, the increased production of PGE 2 resulting from TNF stimulation was blocked by the addition of an interleukin‐1β (IL‐1β) neutralizing antibody, suggesting that TNF regulation of hOB cell PG synthesis was secondary to its capacity to increase hOB cell IL‐1β production. TGFβ regulation of PG production was not affected by the addition of the neutralizing antibody. These studies support the proposition that PGs can be important autocrine/paracrine mediators of bone biology, whose production by hOB cells is responsively regulated by osteotropic cytokines. J. Cell. Biochem. 64:618–631. © 1997 Wiley‐Liss, Inc.