IL-1 Receptor Type II Production Is Upregulated by IL-4 and IL-13, and Downregulated by IFN-γ in Mouse Gingival Epithelial Cells

Abstract

Background and Objective: Interleukin-1 (IL-1) binds to 2 distinct and separate receptors, types I and II (IL-1RI and IL-1RII, respectively). The binding of IL-1 to IL-1RI induces cellular signaling and biological effects, whereas binding to IL-1RII does not induce cellular signaling and indirectly inhibits IL-1 biological activities such as that of the decoy receptor. Recently, Suzukiet al.reported that soluble IL-1RII (sIL-1RII) was detected in gingival crevicular fluid from a periodontitis patient. However, it remains unclear which cells produce sIL-1RII detected in periodontal tissues. We examined the localization of IL-1RII producing cells in gingival tissues as well as related production control mechanisms. Material and Methods: IL-1RII mRNA expression in gingival epithelial cells (GE1) was performed by real-time PCR analysis, while the amount of sIL-1RII production in supernatant from GE1 cells was examined by dot-blot analysis. Involvement of the phosphorylation of STAT6 in the signaling pathway was determined by western blot analysis. Statistical analysis was performed with Student’st-test. Results: Culturing with IL-4 and IL-13 significantly increased IL-1RII mRNA to levels 10.5-and 8.89-fold, respectively, above that of the control (p< 0.01), while addition of interferon-γ (IFN-γ) significantly suppressed IL-1RII mRNA by 0.22-fold as compared to the control (p< 0.05). Soluble IL-1RII in the supernatant of cultured GE1 cells was increased by IL-4 and IL-13, and decreased by IFN-γ, while western blotting determines the suppression of IL-1RII production by IFN-γ. Without the addition of IL-4 or IL-13 with or without IFN-γ, P-Tyr-STAT6 was not detected. Conclusion: IL-1RII mRNA expression and sIL-1RII production were increased by IL-4 and IL-13, and decreased by IFN-γ. Finally, IL-4 signaling was regulated by IFN-γ through phosphorylation of STAT6 and IL-13 signaling blockage by IFN-γ downstream of STAT6 translocation.

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Kamiya, Y. , Ishihara, Y. , Kamei, H. , Ozawa, Y. , Mizutani, H. , Kubo, K. , Maeda, H. and Noguchi, T. (2014) IL-1 Receptor Type II Production Is Upregulated by IL-4 and IL-13, and Downregulated by IFN-γ in Mouse Gingival Epithelial Cells. Modern Research in Inflammation, 3, 37-47. doi: 10.4236/mri.2014.32005.

Conflicts of Interest

The authors declare no conflicts of interest.

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