Transforming Growth factor-beta2 Regulates C3 Secretion in Monocytes Through a Protein Kinase C-dependent Pathway

Mol Immunol. 1998 Jan;35(1):1-11. doi: 10.1016/s0161-5890(98)00014-5.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 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*


  • Complement C3
  • Isoenzymes
  • Isoquinolines
  • Naphthalenes
  • Sulfonamides
  • Transforming Growth Factor beta
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
  • N-(2-guanidinoethyl)-5-isoquinolinesulfonamide
  • Protein Kinase C
  • calphostin C
  • Tetradecanoylphorbol Acetate