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Oncostatin M-induced IL-6 expression in murine fibroblasts requires the activation of protein kinase Cdelta

David C Smyth1, Christine Kerr, Carl D Richards

  • 1Centre for Gene Therapeutics, Department of Pathology and Molecular Medicine, McMaster University, 1200 Main Street West, Hamilton, Ontario, Canada.

Journal of Immunology (Baltimore, Md. : 1950)
|December 5, 2006
PubMed

Insights

Oncostatin M (OSM) up-regulates IL-6 in fibroblasts via a novel PI3K-PKCdelta signaling pathway. This pathway is crucial for OSM

Area of Science:

  • Cellular Biology
  • Immunology
  • Molecular Biology

Background:

  • Oncostatin M (OSM) is a cytokine involved in inflammation and connective tissue metabolism.
  • The precise molecular mechanisms underlying OSM's cellular responses, particularly IL-6 expression, remain incompletely understood.
  • Understanding these pathways is critical for elucidating inflammatory processes.

Purpose of the Study:

  • To investigate the signaling pathways mediating Oncostatin M (OSM)-induced IL-6 expression in murine fibroblasts.
  • To identify the specific protein kinase C (PKC) isoforms and upstream regulators involved in OSM signaling.
  • To elucidate a novel signaling network utilized by OSM in inflammatory processes.

Main Methods:

  • Utilized pharmacological inhibitors targeting various PKC isoforms (pan-PKC, calcium-dependent PKC, PKCdelta).
  • Employed RNA interference (siRNA) to silence specific PKC isoforms (PKCdelta, PKCepsilon) and other signaling molecules (PDK-1, Akt1).
  • Assessed IL-6 expression at both mRNA and protein levels, alongside kinase activity assays.

Main Results:

  • Activation of the novel, calcium-independent PKCdelta isoform is critical for OSM-mediated IL-6 up-regulation.
  • PKCdelta silencing, but not PKCepsilon silencing, abrogated OSM-induced IL-6 secretion.
  • Phosphoinositide 3-kinase (PI3K) is required for PKCdelta activation and subsequent IL-6 expression, independent of PDK-1 or Akt1.

Conclusions:

  • A novel signaling pathway involving PI3K and PKCdelta mediates OSM-induced IL-6 expression in murine fibroblasts.
  • This PI3K-PKCdelta axis represents a key component of OSM's role in inflammatory responses.
  • Findings provide new insights into the molecular mechanisms of cytokine signaling in inflammation.

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