PROTEIN KINASE C-DEPENDENT PATHWAY IS CRITICAL FOR THE PRODUCTION OF PRO-INFLAMMATORY CYTOKINES (TNF-α, IL-1β, IL-6)

The authors hypothesized that certain PKC isoforms play an important role in the induction of pro-inflammatory cytokine (TNF-α, IL-1β, IL-6) synthesis. To test this hypothesis, the cytosol-to-membrane translocation of select PKC isoforms with tested cytokine production in human monocytes cultured in...

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Bibliographic Details
Published in:	Cytokine (Philadelphia, Pa.) Vol. 11; no. 11; pp. 839 - 848
Main Authors:	Kontny, Ewa, ZiÓŁKowska, Maria, Ryżewska, Alicja, Maśliński, Włodzimierz
Format:	Journal Article
Language:	English
Published:	England Elsevier Ltd 01-11-1999
Subjects:	Cells, Cultured Dose-Response Relationship, Drug Enzyme Activation - drug effects Enzyme Inhibitors - pharmacology Humans Interleukin-1 - antagonists & inhibitors Interleukin-1 - biosynthesis Interleukin-1 - genetics Interleukin-6 - antagonists & inhibitors Interleukin-6 - biosynthesis Isoenzymes - metabolism Lipopolysaccharides - pharmacology Mitogen-Activated Protein Kinases - metabolism Monocytes - drug effects Monocytes - enzymology Monocytes - metabolism monocytes/PKC isoforms/pro-inflammatory cytokines Naphthalenes - pharmacology Phosphorylation - drug effects Protein Kinase C - antagonists & inhibitors Protein Kinase C - metabolism Reverse Transcriptase Polymerase Chain Reaction Tetradecanoylphorbol Acetate - pharmacology Transcription Factor AP-1 - antagonists & inhibitors Transcription Factor AP-1 - metabolism Transcription, Genetic - drug effects Tumor Necrosis Factor-alpha - antagonists & inhibitors Tumor Necrosis Factor-alpha - biosynthesis Tumor Necrosis Factor-alpha - genetics monocytes/PKC isoforms/pro-inflammatory cytokines
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Summary:	The authors hypothesized that certain PKC isoforms play an important role in the induction of pro-inflammatory cytokine (TNF-α, IL-1β, IL-6) synthesis. To test this hypothesis, the cytosol-to-membrane translocation of select PKC isoforms with tested cytokine production in human monocytes cultured in vitro was correlated. It is reported that in monocytes treated with phorbol ester (PMA), translocation of PKC isoforms α, βII, δ and ϵ precede cytokine synthesis. Moreover, specific inhibition of PKC translocation that occurs in the presence of Calphostin C is reflected in downstream events: lack of MAP kinases phosphorylation, loss of DNA binding ability by AP-1 transcription factor, and the reduction of pro-inflammatory cytokine synthesis. Thus, the cytosol-to-membrane translocation of PKC isoforms α, βII, δ and ϵ with the subsequent activation of: (1) MAP kinases; and (2) AP-1 transcription factor, may represent critical steps in the induction of signalling cascade leading to TNF-α, IL-1β, IL-6 synthesis in human monocytes.
ISSN:	1043-4666 1096-0023
DOI:	10.1006/cyto.1998.0496