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

Marilyn C. Fernandez, Phillip T. Marucha, Isolde G. Rojas, John D. Walters

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)445-449
Number of pages5
JournalCytokine
Volume12
Issue number5
DOIs
StatePublished - May 2000

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Keywords

  • Gene expression
  • Granulocytemacrophage colony-stimulating factor
  • Interleukin 1
  • Neutrophil

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Biochemistry
  • Hematology
  • Molecular Biology

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