The role of protein kinase C and calcium in induction of human polymorphonuclear leukocyte IL-1β gene expression by GM-CSP

At infection sites, synthesis of interleukin (IL-)1β 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-1β gene expression by GM-CSF. The PKC inhibitors chelerythrine and H7 blocked induction of IL-1β mRNA expression in human PMNs. HA1004, an H7 analogue with little activity towards PKC, had no inhibitory effect. Similarly, H7 blocked IL-1β transcription in nuclear run-on analysis, while HA1004 had little effect. The intracellular Ca²⁺ chelator BAPTA/AM inhibited induction of IL-1β mRNA accumulation and transcription by GM-CSF. At concentrations similar to those used to inhibit IL-1β 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. (C) 2000 Academic Press.