Post from Watsonhelper over on YMB: Scientific
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Scientific Reports 5, Article number: 8133 doi:10.1038/srep08133 Published 02/25 February 2015
These results suggest an inhibitory role for MANF in inflammatory cell proliferation, which support the notion that MANF plays an inhibitory role in the activation of NF-κB target genes.
Mesencephalic astrocyte-derived neurotrophic factor (MANF; also known as ARMET) belongs to the fourth family of neurotrophic factors. MANF protects neurons and alleviates the Parkinson's disease-like symptoms in rat 6-hydroxydopamine model. In non-neuronal cells, MANF has also been identified as a secretion protein induced by ER stress that protects against various forms of ER stress-induced damage17, 18, 19, 20. In this study, we detected MANF expression in the peripheral white blood cells (PWBC) isolated from the patients with rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) and from rabbits with antigen-induced arthritis (AIA). The role of MANF involved in inflammation was also investigated by using primarily cultured fibroblast-like synoviocytes (FLS). Our data demonstrated that MANF functioned as an inhibitor of the NF-κB signaling pathway by blocking the binding of p65 to the promoter of its target genes. Consistently, MANF suppressed the expressions of NF-κB dependent genes. MANF knockdown enhanced the proliferation of inflammatory synoviocytes. Therefore, this study suggests that MANF may be a novel negative regulator of inflammation by interacting with p65