title: Anti-inflammatory effects of recombinant human PDCD5 (rhPDCD5) in a rat collagen-induced model of arthritis.
abstract: 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.
authors.affiliation: Key Laboratory of Medical Immunology, Ministry of Health, Peking University Health Science Center, Beijing, 100191, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Xiao
authors.forename: Ge
authors.initials: G
authors.lastname: Li
authors.forename: Jia
authors.initials: J
authors.lastname: Hu
authors.forename: Liujing
authors.initials: L
authors.lastname: Qu
authors.forename: Dalong
authors.initials: D
authors.lastname: Ma
authors.forename: Yingyu
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D051017:Apoptosis Regulatory Proteins / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D003094:Collagen / Q000633:toxicity; D005260:Female; D006801:Humans; D009363:Neoplasm Proteins / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D051017:Apoptosis Regulatory Proteins; D009363:Neoplasm Proteins; C117283:PDCD5 protein, human; D011994:Recombinant Proteins; D003094:Collagen