Astrocyte inflammation plays important roles both in physiological and pathological processes in the central nervous system (CNS). Ischemic injury in the CNS causes damage to astrocytes and the release of proinflammatory cytokines, such as tumor necrosis factor-α, interleukin-1β, and interleukin-6. This current study investigates whether mesencephalic astrocyte-derived neurotrophic factor (MANF) inhibits oxygen–glucose deprivation (OGD)-induced cell damage and inflammatory cytokine secretion by suppressing endoplasmic reticulum stress in rat primary astrocytes. We found that MANF alleviated OGD-induced astrocyte damage and rescued the cell viability, and the upregulation of GRP78 (endoplasmic reticulum (ER) stress marker) and NF-κB p65 (one of the central mediators of proinflammatory pathways) induced by OGD were significantly reduced by preincubation of MANF. In addition, the increases of secretion and mRNA expression levels of the proinflammatory cytokines IL-1β, IL-6, and TNF-α in astrocytes induced by OGD were significantly suppressed by MANF. These findings demonstrate that MANF shows the potential to alleviate cell damage and inflammation in rat primary astrocytes by suppressing ER stress, indicating that MANF plays an important role in astrocyte inflammation and functioning and may suggest a promising strategy for neuroprotection in the CNS.
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The authors are grateful to Prof. Chen ZY (Department of Neurobiology, Shandong University) and Prof. Tang DQ, Wang XL, Cui TX, Cui ZQ (Research Center for Cell Therapy, Qilu Hospital of Shandong University), for their kind advice and help with this research. The study was supported by a grant from Ph.D. Programs Foundation of Ministry of Education of China (20110131120079).
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