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Interaction between PKR and PACT mediated by LPS-inducible NF-κB in human gingival cells

Kaya Yoshida1, Hirohiko Okamura, Yumi Hoshino

  • 1Departments of Fundamental Oral Health Science, Institute of Health Biosciences, The University of Tokushima Graduate School, 3-18-15 Kuramoto, Tokushima 770-8504, Japan. kaya@dent.tokushima-u.ac.jp

Journal of Cellular Biochemistry
|September 2, 2011
PubMed

Insights

Lipopolysaccharide (LPS) activates PKR and PACT in gingival cells, involving NF-κB in pro-inflammatory cytokine production. PKR itself does not appear to drive cytokine release in periodontitis.

Area of Science:

  • Cell Biology
  • Immunology
  • Oral Biology

Background:

  • Double-stranded RNA-dependent protein kinase (PKR) is a key regulator of cellular responses, including antiviral defense, differentiation, and apoptosis.
  • The role of PKR in the pathogenesis of periodontitis, a chronic inflammatory gum disease, remains unclear.

Purpose of the Study:

  • To investigate the involvement of PKR in lipopolysaccharide (LPS)-induced inflammatory responses in human gingival cells.
  • To elucidate the molecular mechanisms linking LPS, PKR, and pro-inflammatory cytokine production in the context of periodontitis.

Main Methods:

  • Human gingival Sa3 cells were treated with LPS.
  • PKR phosphorylation, PACT expression, NF-κB translocation, and pro-inflammatory cytokine mRNA levels (IL-6, TNFα) were assessed.
  • RNA interference (RNAi) for PKR and pharmacological NF-κB inhibition were employed.

Main Results:

  • LPS treatment induced PKR phosphorylation and PACT upregulation in Sa3 cells.
  • LPS promoted the association between PACT and PKR, dependent on NF-κB translocation.
  • While NF-κB inhibition reduced pro-inflammatory cytokine production, PKR silencing or inhibition did not affect it.

Conclusions:

  • LPS triggers PKR phosphorylation and PACT-PKR complex formation in gingival cells, mediated by NF-κB.
  • NF-κB plays a crucial role in LPS-induced pro-inflammatory cytokine production in periodontitis.
  • PKR does not appear to be essential for the LPS-driven induction of IL-6 and TNFα in this cellular model.

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