CAJ | 학술논문

目的：探讨白细胞介素-22（IL-22）刺激类风湿关节炎滑膜成纤维细胞（RASF）产生白细胞介素-6（IL-6）的水平，及间接调控IL-17＋CD4＋T（Th17）细胞分化的能力。方法分离RASF 6例，建立体外培养体系，IL-22刺激RASF，qRT-PCR及ELISA检测IL-6的表达；IL-22R1封闭抗体及抑制剂实验检测IL-6产生所涉及的特异性受体及其下游信号通路；建立RASF与健康志愿者CD4＋T细胞共培养体系和Transwell 体系，流式细胞术检测体系中各组 Th17细胞比例。结果 IL-22刺激RASF呈时间和剂量依赖性产生IL-6（P＜0．05），且IL-6产生依赖于IL-22R1及其下游的p38和JAK2通路（P＜0．05）；共培养体系和Transwell体系中发现IL-22预刺激RASF组较未刺激组Th17细胞比例增加，阻断IL-22R1或IL-6均能降低Th17细胞比例。结论 IL-22刺激RASF产生IL-6，进而促进Th17细胞分化，中和IL-22是RA治疗的有效策略。
목적：탐토백세포개소-22（IL-22）자격류풍습관절염활막성섬유세포（RASF）산생백세포개소-6（IL-6）적수평，급간접조공IL-17＋CD4＋T（Th17）세포분화적능력。방법분리RASF 6례，건입체외배양체계，IL-22자격RASF，qRT-PCR급ELISA검측IL-6적표체；IL-22R1봉폐항체급억제제실험검측IL-6산생소섭급적특이성수체급기하유신호통로；건립RASF여건강지원자CD4＋T세포공배양체계화Transwell 체계，류식세포술검측체계중각조 Th17세포비례。결과 IL-22자격RASF정시간화제량의뢰성산생IL-6（P＜0．05），차IL-6산생의뢰우IL-22R1급기하유적p38화JAK2통로（P＜0．05）；공배양체계화Transwell체계중발현IL-22예자격RASF조교미자격조Th17세포비례증가，조단IL-22R1혹IL-6균능강저Th17세포비례。결론 IL-22자격RASF산생IL-6，진이촉진Th17세포분화，중화IL-22시RA치료적유효책략。
Objective To investigate the effects of interleukine-22 ( IL-22 ) on the expression of interleukin-6 (IL-6) by rheumatoid arthritis synovial fibroblasts (RASF), and to analyze their association with IL-17+CD4+T (Th17) cells differentiation.Methods RASF were isolated from six patients with rheu-matoid arthritis ( RA) and cultured in vitro.The expression of IL-6 at mRNA and protein levels by RASF were detected by qRT-PCR analysis and ELISA after treatment with different concentrations of IL -22 for dif-ferent periods of time.Anti-IL-22R1 blocking antibody and inhibitor assay were used to analyze the specific receptor and its downstream signaling pathways associated with IL-6 production.IL-22 pre-treated RASF and CD4+T cells were co-cultured for 3 days in the presence or absence of anti-IL-22R1 or anti-IL-6 to measure the percentage of Th 17 cells by flow cytometry .Results The expression of IL-6 by RASF was increased up-on IL-22 stimulation in a dose and time dependent manner (P<0.05), and that was closely related to IL-22R1 and its downstream signaling pathways of p38 and JAK2 (P<0.05).Co-culturing CD4+T cells with RASF and Transwell system indicated that the percentage of Th 17 cells was increased in IL-22 pre-treated group as compared with that in IL-22 untreated group , but it could be down-regulated by either blocking IL-22R1 or IL-6.Conclusion IL-22 promoted the expression of IL-6 by RASF and further enhanced Th 17 dif-ferentiation.Neutralizing IL-22 in synovium of patients with RA might be an effective therapeutic strategy for RA treatment.