Endogenous membrane-bound IL-15 sustains recruitment of IL-2Rβ and common γ through activation of NF-κB in human gingival fibroblasts

Akiko Ozawa, Hiroyuki Tada, Yumiko Sugawara, Akiko Uehara, Takashi Sasano, Hidetoshi Shimauchi, Haruhiko Takada, Shunji Sugawara

Research output: Contribution to journalArticlepeer-review

Abstract

To investigate the role of human gingival fibroblasts (HGF) in periodontitis, we examined the expression of interleukin-2 receptor (IL-2R) and IL-15R subunits in HGF from normal and inflamed regions and the role of endogenous IL-15 in IL-2-mediated signaling. Normal HGF expressed IL-2Rβ and common γ-chain (γc) but not IL-2Rα or IL-15Rα, whereas inflamed HGF expressed IL-2Rα, IL-15Rα, IL-2Rβ and γc. Exogenous IL-2 and IL-15 induced production of monocyte chemoattractant protein-1 (MCP-1) but not IL-8 in normal HGF, and induced the production of both chemokines in inflamed HGF. Both HGF constitutively transcribed 48aa-IL-15 isoform, and the isoform existed as a membrane-bound form. Pretreatment with anti-IL-15 neutralizing mAb completely inhibited the production of MCP-1 induced by IL-2 and IL-15 and IL-2-induced phosphorylation of Janus tyrosine kinase 1 and 3 in HGF. The pretreatment and RNA interference targeted to IL-15 mRNA resulted in total inhibition of the IL-2Rβ and γc expression at mRNA and protein levels. Furthermore, inhibition of nuclear factor (NF)-κB abrogated the expression of IL-2Rβ and γc, and IL-2-induced-nuclear translocation of NF-κB was completely inhibited by the RNA interference in HGF. These results suggest that endogenous membrane-bound IL-15 sustains recruitment of IL-2Rβ and γc through activation of NF-κB in HGF.

Original languageEnglish
Pages (from-to)175-180
Number of pages6
JournalInternational Congress Series
Volume1284
DOIs
Publication statusPublished - 2005 Sep 1

Keywords

  • Cellular activation
  • Cytokine receptors
  • Cytokines
  • Inflammation
  • Mucosa

ASJC Scopus subject areas

  • Medicine(all)

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