Differential regulation of elicited-peritoneal macrophage 14 kDa and 85 kDa phospholipase A2(s) by transforming growth factor-beta.
Elicited guinea pig macrophages collected from inflammatory peritoneal exudate release soluble 14 kDa phospholipase A2 (PLA2) and prostaglandin E2 (PGE2) into surrounding media during culture (Marshall et al. (1994) J. Lipid Med. 10, 295-313). The effect of transformation growth factor beta 1 (TGF beta), an immunoregulatory growth factor, was examined in this system. Exposure of cultured macrophages to TGF beta reduced both the activity and protein levels of 14 kDa PLA2 measured in conditioned media. This inhibition occurred within the first 6-8 h, was prevalent through 72 h of exposure and was dependent on TGF beta concentration. The reduction, however, never reached more than 40-60%. Evaluation of the cellular PLA2 activity confirmed the existence of an immunologically-related 14 kDa PLA2 (ELISA) in the particulate fraction and an 85 kDa PLA2 (Western analysis) in the cytosol. Exposure to TGF beta halved the particulate activity and protein levels of 14 kDa PLA2 which was consistent with the reduction in the secreted form. Alternatively, TGF beta induced an increase in cytosolic 85 kDa PLA2 (activity and protein) which was not apparent until 12 h and significant at 20-24 h of exposure. This demonstrates that TGF beta differentially regulates the production of these two enzymes. Despite this, neither PGE2 synthesis nor the up-regulated cyclooxygenase -II were altered by TGF beta treatment suggesting that maximal prostanoid synthesis had been reached.
Bolognese
B
B
SmithKline Beecham Pharmaceuticals, Inflammation and Respiratory Pharmacology, King of Prussia, PA 19406-0939, USA.
McCord
M
M
Marshall
L A
LA
D000818:Animals; D015232:Dinoprostone / Q000096:biosynthesis; D006168:Guinea Pigs; D007527:Isoenzymes / Q000096:biosynthesis*; D008262:Macrophage Activation; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D010538:Peritonitis / Q000276:immunology; D010741:Phospholipases A / Q000096:biosynthesis*; D054467:Phospholipases A2; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D007527:Isoenzymes; D016212:Transforming Growth Factor beta; D011451:Prostaglandin-Endoperoxide Synthases; D010741:Phospholipases A; D054467:Phospholipases A2; D015232:Dinoprostone