Differential regulation of phospholipase A2 by cytokines inhibiting bone formation and mineralization.
Treatment of fetal rat calvarial cells with interleukin-1 alpha, tumor necrosis factor-alpha, transforming growth factor-beta 1, or group II phospholipase A2 inhibits the number of bone nodules formed in long-term cultures. These same mediators also inhibit the mineralization of fully developed bone nodules in a time and dose-dependent fashion. The pro-inflammatory cytokines interleukin-1 alpha and tumor necrosis factor-alpha cause a dose-dependent induction of rat calvarial cell phospholipase A2-II mRNA levels, suggesting that their effects on bone formation may be mediated indirectly by activation of this enzyme. In contrast, transforming growth factor-beta 1, which has more potent effects on bone formation than interleukin-1 alpha or tumor necrosis factor-alpha, suppresses basal levels of phospholipase A2-II mRNA, indicating a different mechanism of action for this cytokine.
Ellies
L G
LG
MRC Group in Periodontal Physiology, University of Toronto, Canada.
Gupta
A K
AK
Aubin
J E
JE
D000818:Animals; D001483:Base Sequence; D002113:Calcification, Physiologic / Q000187:drug effects*; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D004622:Embryo, Mammalian / Q000166:cytology; D007375:Interleukin-1 / Q000494:pharmacology; D008969:Molecular Sequence Data; D010012:Osteogenesis / Q000187:drug effects*; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D051381:Rats; D011919:Rats, Inbred Strains; D017208:Rats, Wistar; D012886:Skull / Q000166:cytology / Q000201:enzymology*; D014158:Transcription, Genetic / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016207:Cytokines; D007375:Interleukin-1; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D010741:Phospholipases A; D054467:Phospholipases A2