Hosokawa Y, Hosokawa I, Ozaki K, Nakae H, Matsuo T
Department of Conservative Dentistry, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
Clin Exp Immunol. 2007 Jul;149(1):146-54. doi: 10.1111/j.1365-2249.2007.03398.x. Epub 2007 Apr 25.
Periodontal disease is an inflammatory disorder characterized by the involvement of chemokines that are important for the recruitment of leucocytes. Several cytokines are involved in regulating levels of chemokines in periodontal disease. CXCL16 is a chemokine related to the migration of T helper 1 (Th1) cells and natural killer (NK) cells. In this study, we examined its expression in periodontal tissues. Moreover, we investigated the effects of cytokines on the production of CXCL16 by human gingival fibroblast (HGF). Reverse transcription-polymerase chain reaction (RT-PCR) analysis and immunohistochemistry revealed that CXCL16 and its receptor, CXCR6, were expressed at the mRNA and protein levels in diseased tissues. Proinflammatory cytokines [interleukin (IL)-1beta, tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma] increased the mRNA expression and release of CXCL16 in a dose-dependent manner. Moreover, treatment of HGFs with IFN-gamma in combination with IL-1beta had a synergistic effect on the production of CXCL16. On the other hand, IL-4 and IL-13 inhibited the IL-1beta-induced CXCL16 production by HGFs. Inhibitors of A disintegrin and metalloprotease (ADAM)10 and ADAM17, a recently identified protease of CXCL16, reduced the amount of CXCL16 released from HGFs. These results suggest that the CXCL16 produced by HGFs may be involved in the migration of leucocytes into inflamed tissues, and provide evidence that CXCL16 production is controlled by cytokines in periodontal disease.
牙周病是一种炎症性疾病，其特征在于趋化因子的参与，这些趋化因子对白细胞的募集很重要。几种细胞因子参与调节牙周病中趋化因子的水平。CXCL16是一种与辅助性T细胞1（Th1）和自然杀伤（NK）细胞迁移相关的趋化因子。在本研究中，我们检测了其在牙周组织中的表达。此外，我们研究了细胞因子对人牙龈成纤维细胞（HGF）产生CXCL16的影响。逆转录-聚合酶链反应（RT-PCR）分析和免疫组织化学显示，CXCL16及其受体CXCR6在患病组织的mRNA和蛋白质水平上均有表达。促炎细胞因子[白细胞介素（IL）-1β、肿瘤坏死因子（TNF）-α和干扰素（IFN）-γ]以剂量依赖性方式增加CXCL16的mRNA表达和释放。此外，用IFN-γ联合IL-1β处理HGFs对CXCL16的产生具有协同作用。另一方面，IL-4和IL-13抑制HGFs中IL-1β诱导的CXCL16产生。一种新发现的CXCL16蛋白酶——解聚素和金属蛋白酶（ADAM）10和ADAM17的抑制剂，减少了HGFs释放的CXCL16量。这些结果表明，HGFs产生的CXCL16可能参与白细胞向炎症组织的迁移，并提供了牙周病中CXCL16的产生受细胞因子控制的证据。
