Transforming growth factor-beta2 regulates C3 secretion in monocytes through a protein kinase C-dependent pathway

Previously, we reported that TGF-beta2 regulates the C3 gene expression in a dose- and time-dependent manner in monocytes. To extend these studies, we examined the role of PKC in the TGF-beta2-mediated induction of C3 expression by the human monocyte cell line, U937. Treatment of U937 cells with the...

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Bibliographic Details
Published in:Molecular immunology 1998-01, Vol.35 (1), p.1
Main Authors: Drouin, S M, Kiley, S C, Carlino, J A, Barnum, S R
Format: Article
Language:English
Subjects:
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine - pharmacology
Complement C3 - metabolism
Drug Interactions
Humans
Inflammation - immunology
Isoenzymes - metabolism
Isoquinolines - pharmacology
Monocytes - immunology
Naphthalenes - pharmacology
Protein Kinase C - antagonists & inhibitors
Protein Kinase C - metabolism
Signal Transduction
Sulfonamides
Tetradecanoylphorbol Acetate - pharmacology
Transforming Growth Factor beta - pharmacology
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Summary:Previously, we reported that TGF-beta2 regulates the C3 gene expression in a dose- and time-dependent manner in monocytes. To extend these studies, we examined the role of PKC in the TGF-beta2-mediated induction of C3 expression by the human monocyte cell line, U937. Treatment of U937 cells with the PKC inhibitors, H7 and calphostin C, suppressed TGF-beta2-mediated induction of C3 protein levels, but not mRNA levels, in a dose-dependent manner. At the highest concentrations of H7 and calphostin C, C3 protein levels were inhibited 50% and 93%, respectively, compared to control levels. Treatment of U937 cells with HA1004, a weak PKC inhibitor used as a control for H7, did not inhibit induction of C3 protein levels. Down-modulating PKC with a prolonged exposure of U937 cells to PMA also suppressed TGF-beta2-mediated C3 protein induction by as much as 82%. Incubating cell extracts isolated from TGF-beta2-treated U937 cells with the PKC substrate, MIBP(4-14), resulted in increased substrate phosphorylation compared to cell extracts isolated from untreated cells. Addition of calphostin C suppressed the increased substrate phosphorylation by TGF-beta2. Furthermore, biosynthetic labeling of U937 cells treated with TGF-beta2 and calphostin C demonstrated an accumulation of C3 protein within cell lysates compared to controls. Collectively, these studies suggest a role for PKC in the secretion of C3 protein during TGF-beta2-mediated regulation of C3 expression in U937 cells.
ISSN:0161-5890