Wang Wanlin1,2, Mao Chun2, Xiao Juan2. 1. Zaoyang First People's Hospital, Hubei University of Arts and Science, Xiangyang 441200, China. 2. Laboratory of Molecular Medicine, Hubei University of Arts and Science, Xiangyang 441053, China.
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 (20μg/mL) or anti-CD3 (1μg/mL)+ anti-CD28 (2μg/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-γand 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. CONCLUSIONS: 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.
OBJECTIVE: To investigate the effect of recombinant humanPDCD5 (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 (20μg/mL) or anti-CD3 (1μg/mL)+ anti-CD28 (2μg/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-γand 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. CONCLUSIONS: 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.
Entities:
Keywords:
activation-induced cell death; lymphocytes; recombinant human PDCD5; rheumatoid arthritis
Authors: Bruce W Kirkham; Marissa N Lassere; John P Edmonds; Katherine M Juhasz; Paul A Bird; C Soon Lee; Ron Shnier; Ian J Portek Journal: Arthritis Rheum Date: 2006-04
Authors: Mario Mellado; Laura Martínez-Muñoz; Graciela Cascio; Pilar Lucas; José L Pablos; José Miguel Rodríguez-Frade Journal: Front Immunol Date: 2015-07-27 Impact factor: 7.561