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鸡Ⅱ型胶原诱导胶原诱导性关节炎大鼠肠系膜淋巴结淋巴细胞中辅助性 T 细胞主要亚型免疫平衡。

Chicken type II collagen induced immune balance of main subtype of helper T cells in mesenteric lymph node lymphocytes in rats with collagen-induced arthritis.

机构信息

Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immunopharmacology of Education Ministry of China, 230032, Hefei, China.

出版信息

Inflamm Res. 2010 May;59(5):369-77. doi: 10.1007/s00011-009-0109-4. Epub 2009 Oct 28.

Abstract

OBJECTIVE

To investigate the effect of the oral administration of chicken type II collagen (CCII) on T cells from mesenteric lymph node (MLN) lymphocytes in rats with collagen-induced arthritis (CIA).

METHODS

CIA was induced in male Sprague-Dawley rats immunized with CCII in Freund's complete adjuvant. CCII (10, 20, and 40 microg kg(-1) day(-1), i.g. x 7 days) was administered orally to rats from day 14 to 21 after immunization. Arthritis was evaluated by hind paw swelling and polyarthritis index, and MLNs and synovium were harvested for histological examination. Activity of interleukin-2 (IL-2) in MLN lymphocyte supernatant was measured by ConA-induced splenocyte proliferation in C57BL/6J mice, and IL-4, IL-17, and transforming growth factor beta (TGF-beta) levels in MLN lymphocytes were measured by enzyme-linked immunosorbent assay (ELISA). The proportion of CD4(+)CD25(+) Treg cells and Th17 cells was determined by double-color labeling for flow cytometry analysis.

RESULTS

The administration of CCII (10, 20, 40 microg/kg, i.g. x 7 days) suppressed secondary inflammatory reactions and histological changes in CIA model. The activity of IL-2 and IL-17 produced by MLN lymphocytes from CIA rats was significantly inhibited by the administration of CCII (10, 20, and 40 microg kg(-1) day(-1)). The levels of IL-4 and TGF-beta were increased in CCII (10, 20, and 40 microg kg(-1) day(-1)) groups. The flow cytometry analysis showed that CCII (10, 20, and 40 microg kg(-1) day(-1)) significantly increased the proportion of Treg and decreased the proportion of Th17.

CONCLUSION

These results indicate that oral administration of CCII had therapeutic effects on CIA rats, which was related to decreased production of pro-inflammatory mediators (IL-2, IL-17) and increased production of anti-inflammatory mediators (IL-4, TGF-beta). This suggests that CCII plays an important role in regulating the immune balance of Th1/Th2 and Th17/Treg in rats with CIA.

摘要

目的

研究鸡Ⅱ型胶原(CCII)口服给药对胶原诱导关节炎(CIA)大鼠肠系膜淋巴结(MLN)淋巴细胞 T 细胞的影响。

方法

用 CCII 在福氏完全佐剂中免疫雄性 Sprague-Dawley 大鼠诱导 CIA。从免疫后第 14 天至 21 天,每天经口给予 CCII(10、20 和 40μgkg(-1),ig. x 7 天)。通过后爪肿胀和多关节炎指数评估关节炎,并采集 MLN 和滑膜进行组织学检查。通过 C57BL/6J 小鼠 ConA 诱导的脾细胞增殖测量 MLN 淋巴细胞上清液中白细胞介素 2(IL-2)的活性,并通过酶联免疫吸附试验(ELISA)测量 MLN 淋巴细胞中 IL-4、IL-17 和转化生长因子β(TGF-β)的水平。通过双色标记流式细胞术分析确定 CD4(+)CD25(+)Treg 细胞和 Th17 细胞的比例。

结果

CCII(10、20、40μg/kg,ig. x 7 天)给药抑制 CIA 模型中的二次炎症反应和组织学变化。CCII(10、20、40μgkg(-1),ig. x 7 天)给药显著抑制 CIA 大鼠 MLN 淋巴细胞产生的 IL-2 和 IL-17 的活性。CCII(10、20 和 40μgkg(-1))组中 IL-4 和 TGF-β水平增加。流式细胞术分析表明,CCII(10、20 和 40μgkg(-1))给药显著增加了 Treg 的比例,降低了 Th17 的比例。

结论

这些结果表明,CCII 口服给药对 CIA 大鼠具有治疗作用,这与减少促炎介质(IL-2、IL-17)的产生和增加抗炎介质(IL-4、TGF-β)的产生有关。这表明 CCII 在调节 CIA 大鼠 Th1/Th2 和 Th17/Treg 免疫平衡方面发挥重要作用。

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