Xiao Juan, Li Ge, Hu Jia, Qu Liujing, Ma Dalong, Chen Yingyu
Key Laboratory of Medical Immunology, Ministry of Health, Peking University Health Science Center, Beijing, 100191, China.
Inflammation. 2015 Feb;38(1):70-8. doi: 10.1007/s10753-014-0008-x.
Programmed cell death 5 (PDCD5) was first identified as a gene upregulated in cells undergoing apoptosis. We recently demonstrated the inhibitory effect of PDCD5 on experimentally induced autoimmune encephalomyelitis. In this study, we investigated the anti-inflammatory effects of recombinant human PDCD5 (rhPDCD5) in a rat collagen-induced arthritis (CIA) model. We find that vaccination of collagen II (CII) induced CIA rats with rhPDCD5 significantly delayed the occurrence and reduced the severity of CIA rats. rhPDCD5 also restored the loss of Foxp3(+) regulatory T (Treg) cells and decreased the population of Th1 and Th17 in CIA rats. Simultaneously, rhPDCD5 treatment suppressed the production of pro-inflammatory cytokines (interleukin (IL)-6, IL-17A, tumor necrosis factor-α (TNF-α), and interferon gamma (IFN-γ)) and increased the secretion of anti-inflammatory cytokines (transforming growth factor beta 1 (TGF-β1) and IL-10) in CIA rats. In addition, rhPDCD5 inhibited the ability of CII to induce proliferation of splenocytes and lymph node cells (LNCs) and promoted the CII-activated CD4(+) cell apoptosis. These results of rhPDCD5-treated CIA rats were similar with those of recombinant human TNF-α receptor IgG Fc (rhTNFR:Fc). Thus, to our knowledge, we provide the first evidence that rhPDCD5 may be an efficient approach to diminishing exacerbated immune responses in CIA, indicating its therapeutic potential in the treatment of rheumatoid arthritis and other autoimmune diseases.
程序性细胞死亡5（PDCD5）最初被鉴定为在经历细胞凋亡的细胞中上调的基因。我们最近证明了PDCD5对实验性自身免疫性脑脊髓炎的抑制作用。在本研究中，我们在大鼠胶原诱导的关节炎（CIA）模型中研究了重组人PDCD5（rhPDCD5）的抗炎作用。我们发现用rhPDCD5对II型胶原（CII）诱导的CIA大鼠进行接种显著延迟了CIA大鼠的发病并降低了其严重程度。rhPDCD5还恢复了CIA大鼠中Foxp3（+）调节性T（Treg）细胞的缺失，并减少了Th1和Th17细胞的数量。同时，rhPDCD5治疗抑制了促炎细胞因子（白细胞介素（IL）-6、IL-17A、肿瘤坏死因子-α（TNF-α）和干扰素-γ（IFN-γ））的产生，并增加了CIA大鼠中抗炎细胞因子（转化生长因子β1（TGF-β1）和IL-10）的分泌。此外，rhPDCD5抑制了CII诱导脾细胞和淋巴结细胞（LNCs）增殖的能力，并促进了CII激活的CD4（+）细胞凋亡。rhPDCD5治疗的CIA大鼠的这些结果与重组人TNF-α受体IgG Fc（rhTNFR:Fc）的结果相似。因此，据我们所知，我们提供了第一个证据，表明rhPDCD5可能是减轻CIA中加剧的免疫反应的有效方法，表明其在类风湿性关节炎和其他自身免疫性疾病治疗中的治疗潜力。
