TY - JOUR
T1 - Endogenous membrane-bound IL-15 sustains recruitment of IL-2Rβ and common γ through activation of NF-κB in human gingival fibroblasts
AU - Ozawa, Akiko
AU - Tada, Hiroyuki
AU - Sugawara, Yumiko
AU - Uehara, Akiko
AU - Sasano, Takashi
AU - Shimauchi, Hidetoshi
AU - Takada, Haruhiko
AU - Sugawara, Shunji
PY - 2005/9/1
Y1 - 2005/9/1
N2 - 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.
AB - 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.
KW - Cellular activation
KW - Cytokine receptors
KW - Cytokines
KW - Inflammation
KW - Mucosa
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UR - http://www.scopus.com/inward/citedby.url?scp=33646461562&partnerID=8YFLogxK
U2 - 10.1016/j.ics.2005.06.024
DO - 10.1016/j.ics.2005.06.024
M3 - Article
AN - SCOPUS:33646461562
VL - 1284
SP - 175
EP - 180
JO - International Congress Series
JF - International Congress Series
SN - 0531-5131
ER -