The role of protein kinase C and calcium in induction of human polymorphonuclear leukocyte IL-1 beta gene expression by GM-CSF.
At infection sites, synthesis of interleukin (IL-)1beta by polymorphonuclear leukocytes (PMNs) facilitates the recruitment of inflammatory cells and enhances the inflammatory response. We investigated the role of protein kinase C (PKC) and Ca2+ in the induction of PMN IL-1beta gene expression by GM-CSF. The PKC inhibitors chelerythrine and H7 blocked induction of IL-1beta mRNA expression in human PMNs. HA1004, an H7 analogue with little activity towards PKC, had no inhibitory effect. Similarly, H7 blocked IL-1beta transcription in nuclear run-on analysis, while HA1004 had little effect. The intracellular Ca2+ chelator BAPTA/AM inhibited induction of IL1beta mRNA accumulation and transcription by GM-CSF. At concentrations similar to those used to inhibit IL-1beta gene expression, H7, chelerythrine, and BAPTA all inhibited substrate phosphorylation by PKC isolated from PMN lysates. Thus, PKC and Ca2+ are potential targets for modulating an important PMN immunoregulatory function.
Fernandez
M C
MC
Department of Medical Microbiology and Immunology, College of Medicine, The Ohio State University Health Sciences Center, Columbus, USA.
Marucha
P T
PT
Rojas
I G
IG
Walters
J D
JD
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000494:pharmacology; D000470:Alkaloids; D053119:Benzophenanthridines; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology / Q000494:pharmacology; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics*; D007424:Intracellular Fluid / Q000378:metabolism; D007546:Isoquinolines / Q000494:pharmacology; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D010617:Phenanthridines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D011994:Recombinant Proteins; D013449:Sulfonamides; D014158:Transcription, Genetic / Q000187:drug effects
D000470:Alkaloids; D053119:Benzophenanthridines; D004791:Enzyme Inhibitors; D007375:Interleukin-1; D007546:Isoquinolines; D010617:Phenanthridines; D011994:Recombinant Proteins; D013449:Sulfonamides; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C043204:N-(2-guanidinoethyl)-5-isoquinolinesulfonamide; C016299:chelerythrine; D011493:Protein Kinase C; D002118:Calcium