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 language | English (US) |
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Pages (from-to) | 445-449 |
Number of pages | 5 |
Journal | Cytokine |
Volume | 12 |
Issue number | 5 |
DOIs | |
State | Published - May 2000 |
Externally published | Yes |
Keywords
- Gene expression
- Granulocytemacrophage colony-stimulating factor
- Interleukin 1
- Neutrophil
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
- Biochemistry
- Hematology
- Molecular Biology