Recombinant human lymphotoxin effects on osteoblastic cells.
Lymphotoxin, or tumor necrosis factor beta, has been shown to be a potent bone resorbing cytokine. In the present study, the effect of recombinant human lymphotoxin on osteoblastic cell proliferation and prostaglandin synthesis was investigated. Lymphotoxin (10(-10)-10(-7) M) caused a significant, dose-dependent decrease of rat osteoblastic cell proliferation. This appeared to be an indirect, prostaglandin-dependent action, since in the presence of indomethacin (1 microM) the lymphotoxin effect was reversed. Subsequently, prostaglandin E2 and prostacyclin (assayed as 6-keto-prostaglandin F1 alpha) levels produced by the osteoblastic cells in response to lymphotoxin were measured. The cytokine caused a dose-dependent increase of these arachidonic acid metabolites, with the maximum effect at 10(-8) M. These results suggest that lymphotoxin's mechanism of action on bone may involve increases in arachidonic acid metabolite synthesis and an indirect, prostanoid-mediated decrease in the proliferation rate of osteoblastic cells.
Tatakis
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DN
Department of Oral Biology, School of Dental Medicine, State University of New York, Buffalo 14214.
Dziak
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R
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D015232:Dinoprostone / Q000096:biosynthesis; D008233:Lymphotoxin-alpha / Q000494:pharmacology*; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D011460:Prostaglandins F / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000494:pharmacology; D012886:Skull
D008233:Lymphotoxin-alpha; D011460:Prostaglandins F; D011994:Recombinant Proteins; D004247:DNA; D015232:Dinoprostone; C100006:prostaglandin F1