Expression of PKCη in NIH-3T3 cells promotes production of the pro-inflammatory cytokine interleukin-6

Eyal Fima, Galit Shahaf, Tzippi Hershko, Ron N. Apte, Etta Livneh

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


Protein kinase C encodes a family of enzymes implicated in cellular differentiation, growth control and tumor promotion. The generation and characterization of NIH-3T3 cells which stably overexpress the PKCη isoform has been previously described by us. In these cells, overexpression of PKCη altered the expression of specific cell cycle regulators and promoted differentiation [20]. Since PKC has been implicated in the regulation of gene expression, including that of various cytokines, we examined the production of several cytokines in these cells. We report here that out of the major pro-inflammatory cytokines examined, IL-1α, IL-1β, TNF-α and IL-6, only IL-6 was generated and secreted in PKCη-expressing cells without any additional inducer in serum-supplemented cultures (10% FCS). IL-6 was not detected in the control cell line, transfected with the same vector, but lacking the cDNA coding for PKCη. Moreover, the production of IL-6 on serum stimulation correlated with the levels of PKCη expressed in these cells. This implies that factors in the serum activate PKCη and induce IL-6 production. We have examined several growth factors and cytokines for their ability to induce IL-6 production in our PKCη-expressing cells. Among the growth factors tested (EGF, PDGF, FGF, insulin, IGF-1 and IL-1), PDGF and FGF were the most potent IL-6 inducers. The effects of FGF and PDGF on IL-6 production were blocked in the presence of PKC inhibitors. We also examined the signaling pathways that mediate production of IL-6 in PKCη-expressing cells. Using specific inhibitors of the MAPK pathway, we have shown a role for ERK and p38 MAPK in FGF- and serum-stimulated IL-6 production, but only for p38 MAPK in PDGF-stimulated IL-6 production. Our studies provide evidence that PDGF and FGF can serve as upstream regulators of PKCη and that PKCη is involved in the expression of IL-6. This suggests that inhibition of PKC may provide a basis for the development of drugs for the treatment of disorders in which IL-6 is pathologically involved.

Original languageEnglish
Pages (from-to)491-499
Number of pages9
JournalEuropean Cytokine Network
Issue number4
StatePublished - 1 Jan 1999


  • FGF
  • IL-6
  • PDGF
  • PKC
  • Phorbol esters

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Clinical Biochemistry


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