Itraconazole inhibits TNF-alpha-induced CXCL10 expression in oral fibroblasts

作者：Ohta K^*; Ishida Y; Fukui A; Nishi H; Naruse T; Takechi M; Kamata N

来源：Oral Diseases, 2015, 21(1): 106-112.

DOI：10.1111/odi.12226

• itraconazole
• TNF-
• CXCL10
• oral fibroblasts

ObjectiveItraconazole (ICZ) has a broad spectrum of antifungal activity including a wide range of Candida spp. TNF-, an inflammatory cytokine associated with Th1-mediated oral inflammatory disease, enhances inflammatory mediators, such as CXCR3-agonistic chemokines including CXCL10. We examined the anti-inflammatory potential of ICZ against TNF--induced chemokines in oral fibroblasts.
Materials and methodsWe investigated the effects of ICZ on mRNA expressions of various TNF--induced chemokines in immortalized oral keratinocytes (RT7) and oral fibroblasts (GT1) using quantitative PCR analysis. Subsequently, the effects of ICZ and fluconazole (FLZ) on TNF--induced CXCL10 proteins in GT1 and primary fibroblasts were examined using enzyme-linked immunosorbent assays (ELISA). The effect of ICZ on signal transduction protein phosphorylation involved in CXCL10 production from TNF--stimulated GT1 was examined by western blotting.
ResultsICZ inhibited TNF--induced CXCL10 mRNA in GT1, but not RT7. Although ICZ did not affect TNF--induced IL-8 mRNA, the mRNAs of TNF--induced CXCR3-agonistic chemokines such as CXCL9 and CXCL11 were inhibited by ICZ in GT1. TNF--induced CXCL10 protein production in GT1 and primary fibroblasts was inhibited by ICZ, but not FLZ. Finally, ICZ inhibited TNF--induced phosphorylation of c-JUN, which is related to CXCL10 production by TNF--stimulated GT1.
ConclusionICZ may be useful as therapy for Th1-mediated oral inflammatory disease.

• 出版日期2015-1