Endogenous IL-15 sustains recruitment of IL-2Rβ and common γ and IL-2-mediated chemokine production in normal and inflamed 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

16 Citations (Scopus)

Abstract

We recently reported that anti-IL-15 neutralizing mAb has been shown to inhibit production of MCP-1 in response to IL-2 from normal human gingival fibroblasts (HGF), the major constituent of gingival tissue. In the present study, we examined the expression of DL-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, as assessed by RT-PCR and flow cytometry. Exogenous IL-2 and IL-15 induced production of MCP-1 bat not IL-8 in normal HGF, and induced the production of both chemokines in inflamed HGF. Both HGF constitutively transcribed the 48 aa-IL-15 isoform, and the isoform was not actively secreted but rather existed as a membrane-bound form. Pretreatment with anti-IL-15 neutralizing mAb for 24 h completely inhibited the production of MCP-1 induced by IL-2 and IL-15 and IL-2-induced phosphorylation of Jak 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, excess amounts of IL-2 restored the inhibitory effect of anti-IL-15, inhibition of 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)5180-5188
Number of pages9
JournalJournal of Immunology
Volume173
Issue number8
DOIs
Publication statusPublished - 2004 Oct 15

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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