[1]王万林,毛春,肖娟.人重组蛋白PDCD5抑制胶原诱导性关节炎大鼠来源的淋巴细胞增殖和炎性细胞因子分泌并促进活化的淋巴细胞凋亡[J].南方医科大学学报,2019,(06):627.[doi:10.12122/j.issn.1673-4254.2019.06.01]
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人重组蛋白PDCD5抑制胶原诱导性关节炎大鼠来源的淋巴细胞增殖和炎性细胞因子分泌并促进活化的 淋巴细胞凋亡()
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《南方医科大学学报》[ISSN:1673-4254/CN:44-1627/R]

卷:
期数:
2019年06期
页码:
627
栏目:
出版日期:
2019-06-16

文章信息/Info

Title:
rhPDCD5 suppresses pro-inflammatory cytokine secretion and proliferation and induces apoptosis of activated lymphocytes from rats with collagen-induced arthritis
作者:
王万林毛春肖娟
关键词:
人重组蛋白PDCD5淋巴细胞活化诱导性凋亡类风湿性关节炎
Keywords:
recombinant human PDCD5 lymphocytes activation-induced cell death rheumatoid arthritis
DOI:
10.12122/j.issn.1673-4254.2019.06.01
摘要:
目的研究腹腔注射人重组蛋白PDCD5(rhPDCD5)对胶原诱导性关节炎(CIA)大鼠脾脏来源的活化淋巴细胞的作用,探 讨rhPDCD5对活化的脾细胞发挥免疫抑制作用的机制。方法将雌性Wistar大鼠随机分为正常对照组,CIA动物模型+卵白蛋 白(OVA)治疗组,CIA动物模型+rhTNFR:Fc治疗组,CIA动物模型+ rhPDCD5治疗组。第0天建立胶原诱导性类风湿性关节炎 大鼠模型,第2 天到26 天腹腔注射给药。第28 天取脾脏制成单细胞悬液,体外用CII (20 μg/mL)和anti-CD3 (1 μg/mL)+anti- CD28(2 μg/mL)分别刺激活化48 h和72 h。ELISA检测细胞上清中细胞因子干扰素-γ(IFN-γ)和白介素-17A(IL-17A)的水平; [3H]掺入法检测活化脾细胞的增殖;流式细胞技术检测活化的CD4+ T淋巴细胞的凋亡。结果rhPDCD5处理的CIA大鼠来源 的脾细胞经CII和anti-CD3+anti-CD28分别刺激活化之后,分泌的细胞因子IFN-γ 和IL-17A水平下降,增殖能力下降,CD4+ T 淋巴细胞凋亡百分比上调。结论rhPDCD5通过抑制活化的脾细胞分泌炎性细胞因子,抑制活化的脾细胞增殖,促进活化的 CD4+ T淋巴细胞凋亡多条途径发挥免疫抑制作用。
Abstract:
Objective To investigate the effect of recombinant human PDCD5 (rhPDCD5) treatment in a rat model of bovine II collagen (CII)-induced arthritis (CIA) on inflammatory cytokine secretion, proliferation and apoptosis of activated lymphocytes and explore the mechanisms of rhPDCD5-induced immunosuppression on activated lymphocytes. Methods Female Wistar rats were randomly divided into normal control group, CIA+ ovalbumin (OVA) group, CIA+ rhTNFR: Fc group, and CIA+rhPDCD5 group. The rats in the latter 3 groups received intraperitoneal injections of OVA (14 mg/kg), rhTNFR: Fc (3.5 mg/kg) or rhPDCD5 (14 mg/kg) from day 2 to day 26 following CII injection. On day 28, the spleens of the rats were harvested for preparing single cell suspensions of splenocytes, which were activated by CII (20 μg/mL) or anti-CD3 (1 μg/mL)+ anti-CD28 (2 μg/mL) for 48 h and 72 h. The production of interferon-γ (IFN-γ) and interleukin-17A (IL-17A) by the activated lymphocytes was determined by ELISA of the culture supernatants. The proliferation and apoptosis of the activated lymphocytes were assessed using [3H]-thymidine incorporation assay and flow cytometry, respectively. Results Compared with those in CIA + OVA group, IFN-γ and IL-17A secretions by the activated lymphocytes from rhPDCD5-treated CIA rats significantly decreased. RhPDCD5 treatment of the CIA rats obviously suppressed the proliferation and promoted apoptosis of the lymphocytes activated by CII or by anti-CD3 + anti-CD28. Conclusion rhPDCD5 reduces pro-inflammatory cytokine secretion, inhibits the proliferation and promotes activation-induced cell death of activated CD4 + lymphocytes to produce immunosuppression in rat models of CIA.

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更新日期/Last Update: 1900-01-01