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The role of protein kinase C in interleukin 1 and tumor necrosis factor alpha induction of fibroblasts to produce and release granulocyte-macrophage colony-stimulating activity.
Exp Hematol. 1990 Sep; 18(8):888-92.EH

Abstract

The process of signal transduction by interleukin 1 (IL-1) or tumor necrosis factor alpha (TNF alpha) for the production of hematopoietic growth factors by cultured fibroblasts was studied using inhibitors for protein kinase C, cyclic nucleotide-dependent protein kinases, calmodulin-dependent protein kinases, and the Na(+)-H+ antiport system. The protein kinase C inhibitor H-7 was shown to inhibit both IL-1 beta- and TNF alpha-induced granulocyte-macrophage colony-stimulating activity (GM-CSA) production and release from cultured fibroblasts in a dose-dependent manner, with 40 microM H-7 demonstrating maximum suppression of the GM-CSA response. In addition, 100-200 nM staurosporine, a more potent inhibitor of protein kinase C, also completely suppressed GM-CSA from IL-1 beta- and TNF alpha-induced fibroblasts. In contrast, a potent inhibitor of cyclic nucleotide-dependent protein kinases, HA1004, showed no effect when used at 10-40 microM. In addition, an inhibitor of calmodulin-induced protein kinases, W-7, also showed no effect when used at 10-30 microM. Prior incubation with H-7 did not inhibit the ability of fibroblasts to subsequently respond to IL-1 beta or TNF alpha, nor did H-7 directly inhibit the granulocyte-macrophage colony-forming assay. Both dibutyryl cyclic adenosine monophosphate (10-30 microM) and forskolin (1-100 nM), activators of adenylate cyclase, in the presence or absence of the phosphodiesterase inhibitor isobutylmethylxanthine, failed to stimulate a GM-CSA response from cultured fibroblasts, indicating a lack of effect of cyclic nucleotide-dependent protein kinases. Furthermore, the addition of H-7 30 min after induction with IL-1 beta or TNF alpha showed little effect on the synthesis of GM-CSA by cultured fibroblasts, indicating that the signal transduction process probably occurred within the first 30 min of ligand-receptor interaction. Finally, amelioride, an inhibitor of the Na(+)-H+ antiport, was shown to inhibit IL-1 beta-induced GM-CSA in a dose-dependent manner.

Authors+Show Affiliations

Department of Medicine, University of Florida, Gainesville 32610.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

2167234

Citation

Zucali, J R., et al. "The Role of Protein Kinase C in Interleukin 1 and Tumor Necrosis Factor Alpha Induction of Fibroblasts to Produce and Release Granulocyte-macrophage Colony-stimulating Activity." Experimental Hematology, vol. 18, no. 8, 1990, pp. 888-92.
Zucali JR, Morse C, Dinarello CA. The role of protein kinase C in interleukin 1 and tumor necrosis factor alpha induction of fibroblasts to produce and release granulocyte-macrophage colony-stimulating activity. Exp Hematol. 1990;18(8):888-92.
Zucali, J. R., Morse, C., & Dinarello, C. A. (1990). The role of protein kinase C in interleukin 1 and tumor necrosis factor alpha induction of fibroblasts to produce and release granulocyte-macrophage colony-stimulating activity. Experimental Hematology, 18(8), 888-92.
Zucali JR, Morse C, Dinarello CA. The Role of Protein Kinase C in Interleukin 1 and Tumor Necrosis Factor Alpha Induction of Fibroblasts to Produce and Release Granulocyte-macrophage Colony-stimulating Activity. Exp Hematol. 1990;18(8):888-92. PubMed PMID: 2167234.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The role of protein kinase C in interleukin 1 and tumor necrosis factor alpha induction of fibroblasts to produce and release granulocyte-macrophage colony-stimulating activity. AU - Zucali,J R, AU - Morse,C, AU - Dinarello,C A, PY - 1990/9/1/pubmed PY - 1990/9/1/medline PY - 1990/9/1/entrez SP - 888 EP - 92 JF - Experimental hematology JO - Exp Hematol VL - 18 IS - 8 N2 - The process of signal transduction by interleukin 1 (IL-1) or tumor necrosis factor alpha (TNF alpha) for the production of hematopoietic growth factors by cultured fibroblasts was studied using inhibitors for protein kinase C, cyclic nucleotide-dependent protein kinases, calmodulin-dependent protein kinases, and the Na(+)-H+ antiport system. The protein kinase C inhibitor H-7 was shown to inhibit both IL-1 beta- and TNF alpha-induced granulocyte-macrophage colony-stimulating activity (GM-CSA) production and release from cultured fibroblasts in a dose-dependent manner, with 40 microM H-7 demonstrating maximum suppression of the GM-CSA response. In addition, 100-200 nM staurosporine, a more potent inhibitor of protein kinase C, also completely suppressed GM-CSA from IL-1 beta- and TNF alpha-induced fibroblasts. In contrast, a potent inhibitor of cyclic nucleotide-dependent protein kinases, HA1004, showed no effect when used at 10-40 microM. In addition, an inhibitor of calmodulin-induced protein kinases, W-7, also showed no effect when used at 10-30 microM. Prior incubation with H-7 did not inhibit the ability of fibroblasts to subsequently respond to IL-1 beta or TNF alpha, nor did H-7 directly inhibit the granulocyte-macrophage colony-forming assay. Both dibutyryl cyclic adenosine monophosphate (10-30 microM) and forskolin (1-100 nM), activators of adenylate cyclase, in the presence or absence of the phosphodiesterase inhibitor isobutylmethylxanthine, failed to stimulate a GM-CSA response from cultured fibroblasts, indicating a lack of effect of cyclic nucleotide-dependent protein kinases. Furthermore, the addition of H-7 30 min after induction with IL-1 beta or TNF alpha showed little effect on the synthesis of GM-CSA by cultured fibroblasts, indicating that the signal transduction process probably occurred within the first 30 min of ligand-receptor interaction. Finally, amelioride, an inhibitor of the Na(+)-H+ antiport, was shown to inhibit IL-1 beta-induced GM-CSA in a dose-dependent manner. SN - 0301-472X UR - https://www.unboundmedicine.com/medline/citation/2167234/The_role_of_protein_kinase_C_in_interleukin_1_and_tumor_necrosis_factor_alpha_induction_of_fibroblasts_to_produce_and_release_granulocyte_macrophage_colony_stimulating_activity_ L2 - https://antibodies.cancer.gov/detail/CPTC-IL1A-1 DB - PRIME DP - Unbound Medicine ER -