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.
J Periodontal Res. 2009 Apr;44(2):225-31. doi: 10.1111/j.1600-0765.2008.01124.x. Epub 2008 Oct 7.
CXC chemokine 10 (CXCL10) activates CXC chemokine receptor 3 (CXCR3) and attracts activated T-helper 1 cells. In this study we examined the effects of cytokines on CXCL10 production by human gingival fibroblasts.
Human gingival fibroblasts were exposed to pro-inflammatory cytokines (interleukin-1beta, tumor necrosis factor-alpha), a T-helper 1 cytokine (interferon-gamma), T-helper 2 cytokines (interleukin-4, interleukin-13), T-helper 17 cytokines (interleukin-17A, interleukin-22) and regulatory T-cell cytokines (interleukin-10, transforming growth factor-beta1) for 24 h. CXCL10 production by human gingival fibroblasts was examined by enzyme-linked immunosorbent assay.
Human gingival fibroblasts produced CXCL10 protein upon stimulation with interleukin-1beta, tumor necrosis factor-alpha and interferon-gamma. Treatment of human gingival fibroblasts with interferon-gamma in combination with tumor necrosis factor-alpha or interleukin-1beta resulted in a synergistic production of CXCL10. However, interleukin-4 and interleukin-13 inhibited CXCL10 production by interferon-gamma-stimulated or tumor necrosis factor-alpha-stimulated-human gingival fibroblasts. On the other hand, interleukin-17A and interleukin-22 enhanced CXCL10 production by human gingival fibroblasts treated with interferon-gamma and inhibited CXCL10 production by tumor necrosis factor-alpha-stimulated human gingival fibroblasts. Furthermore, the anti-inflammatory cytokine, interleukin-10, inhibited CXCL10 production by both interferon-gamma- and tumor necrosis factor-alpha-stimulated human gingival fibroblasts, but transforming growth factor-beta1 enhanced interferon-gamma-mediated CXCL10 production by human gingival fibroblasts.
These results mean that the balance of cytokines in periodontally diseased tissue may be essential for the control of CXCL10 production by human gingival fibroblasts, and the production of CXCL10 might be important for the regulation of T-helper 1 cell infiltration in periodontally diseased tissue.
CXC趋化因子10（CXCL10）激活CXC趋化因子受体3（CXCR3）并吸引活化的辅助性T1细胞。在本研究中，我们检测了细胞因子对人牙龈成纤维细胞产生CXCL10的影响。
将人牙龈成纤维细胞暴露于促炎细胞因子（白细胞介素-1β、肿瘤坏死因子-α）、辅助性T1细胞因子（干扰素-γ）、辅助性T2细胞因子（白细胞介素-4、白细胞介素-13）、辅助性T17细胞因子（白细胞介素-17A、白细胞介素-22）和调节性T细胞因子（白细胞介素-10、转化生长因子-β1）24小时。通过酶联免疫吸附测定法检测人牙龈成纤维细胞产生CXCL10的情况。
人牙龈成纤维细胞在受到白细胞介素-1β、肿瘤坏死因子-α和干扰素-γ刺激后产生CXCL10蛋白。用干扰素-γ联合肿瘤坏死因子-α或白细胞介素-1β处理人牙龈成纤维细胞会导致CXCL10的协同产生。然而，白细胞介素-4和白细胞介素-13抑制干扰素-γ刺激或肿瘤坏死因子-α刺激的人牙龈成纤维细胞产生CXCL10。另一方面，白细胞介素-17A和白细胞介素-22增强了用干扰素-γ处理的人牙龈成纤维细胞产生CXCL10的能力，并抑制肿瘤坏死因子-α刺激的人牙龈成纤维细胞产生CXCL10。此外，抗炎细胞因子白细胞介素-10抑制干扰素-γ和肿瘤坏死因子-α刺激的人牙龈成纤维细胞产生CXCL10，但转化生长因子-β1增强了干扰素-γ介导的人牙龈成纤维细胞产生CXCL10的能力。
这些结果表明，牙周病组织中细胞因子的平衡对于控制人牙龈成纤维细胞产生CXCL10可能至关重要，并且CXCL10的产生对于调节牙周病组织中辅助性T1细胞的浸润可能很重要。
