Differential regulation of soluble interleukin 1 release and membrane expression by pharmacologic agents.
Membrane IL-1 (mIL-1) expression was compared with release of soluble IL-1 (sIL-1) by C3H/HeNCrl mouse peritoneal macrophages. Selective antagonists of protein kinase C (PKC) (H-7) and calmodulin (W-7) in combination inhibited LPS-induced mIL-1 and sIL-1 production, suggesting a role for these activation pathways in IL-1 induction. Low levels of A23187, when combined with OAG (a direct activator of PKC), stimulated mIL-1 expression in the absence of sIL-1 release. Induction of mIL-1 by LPS was inhibited by PGE2 and dibutyryl cAMP, but higher concentrations were required to inhibit mIL-1 expression compared with sIL-1 release. LTB4 alone did not induce mIL-1 or sIL-1 production. LTB4 did enhance LPS-induced mIL-1 expression but not sIL-1 release. These results indicate that mIL-1 expression and sIL-1 release are differentially regulated. Membrane IL-1 is induced by lower levels of certain stimuli and is less effectively inhibited than is sIL-1 release. This differential regulation is further evidence to support the existance of membrane IL-1.
Brandwein
S R
SR
Rheumatic Disease Unit, Montreal General Hospital Research Institute, McGill University, Quebec, Canada.
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000818:Animals; D000906:Antibodies / Q000276:immunology; D000001:Calcimycin / Q000494:pharmacology; D002147:Calmodulin / Q000037:antagonists & inhibitors; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004075:Diglycerides / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism*; D007546:Isoquinolines / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D007975:Leukotriene B4 / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D009712:Nucleotides, Cyclic / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D012995:Solubility; D013449:Sulfonamides / Q000494:pharmacology; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects
D000906:Antibodies; D002147:Calmodulin; D004075:Diglycerides; D007375:Interleukin-1; D007546:Isoquinolines; D009712:Nucleotides, Cyclic; D010879:Piperazines; D013449:Sulfonamides; D007975:Leukotriene B4; D000001:Calcimycin; C017967:W 7; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C038237:1-oleoyl-2-acetylglycerol; D007770:L-Lactate Dehydrogenase; D011493:Protein Kinase C; D015232:Dinoprostone