Author: Shen, Zu T.; Sigalov, Alexander B.
Title: SARS Coronavirus Fusion Peptide-Derived Sequence Suppresses Collagen-Induced Arthritis in DBA/1J Mice Document date: 2016_6_28
ID: 10wcqgaq_21_1
Snippet: anti-arthritic activities demonstrated in animal models of autoimmune arthritis for TCR CP 20,21,23 and HIV gp41 FP 18 , the SARS-CoV FP-derived peptide sequence MG11 significantly suppresses CIA in mice: the peptide at 25 mg/kg/day inhibits inflammation in CIA as assessed by clinical evaluation and scoring of the disease (Fig. 2) . Histological analysis of the joints reveals that MG11 substantially reduces joint inflammation, protects against ca.....
Document: anti-arthritic activities demonstrated in animal models of autoimmune arthritis for TCR CP 20,21,23 and HIV gp41 FP 18 , the SARS-CoV FP-derived peptide sequence MG11 significantly suppresses CIA in mice: the peptide at 25 mg/kg/day inhibits inflammation in CIA as assessed by clinical evaluation and scoring of the disease (Fig. 2) . Histological analysis of the joints reveals that MG11 substantially reduces joint inflammation, protects against cartilage damage, abrogates bone erosion and reduces systemic bone loss (Figs 3 and 4) The effect is specific as the control MG11-2G peptide administered daily at the same dose of 25 mg/kg does not affect CIA. Incorporation of MG11 into sHDL reduces the effective dosage of the peptide: MG11 in free form at 25 mg/kg/day and sHDL-bound MG11 at 2.5 mg/kg/day show similar anti-arthritic effects in CIA both clinically and histologically. Interestingly, mice treated with free MG11 at a daily dose of 2.5 mg/kg did not exhibit any significant disease improvement as compared to vehicle-treated mice (not shown). At the molecular level, activated T cells mediate production of multiple cytokines and growth factors that are known to be involved in the pathogenesis of RA 57 . Many of these molecules serve as targets of cytokine-blocking therapies that are currently in development (e.g., IL-21, IL-23, and IL-33), at different phases of clinical trials (e.g., IL-7, IL-15, IL-17, and M-CSF) or approved (e.g., TNFα , IL-6, and IL-1 blockers) 57 . In the present study, significantly reduced serum cytokine levels were observed in mice treated with MG11 as compared to vehicle-treated arthritic mice or mice treated with MG11-2G (Fig. 5) . Colocalization of MG11 with TCR in the T cell membrane (Supplemental Fig. 1 ) further supports the suggested molecular mechanisms of the observed immunomodulatory activity of the peptide. These findings are consistent with those previously reported for TCR CP and HIV gp41 FP 18, 58 .
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