Neuroprotective Peptide Humanin Inhibits Inflammatory Response in Astrocytes Induced by Lipopolysaccharide

Humanin (HN) has been proved to be an extensive neuroprotective peptide against AD-related and unrelated insults, but little is know about the effect of HN in inflammation response. Current studies indicated the receptors of HN have a close relationship with immune system, which led us to hypothesize HN might have a role in inflammatory response. In this study, we used lipopolysaccharide (LPS) to induce astrocyte inflammation response. This model in vitro allowed us to study the effect of HN on the pure response of astrocyte without the exogenous influence between cells in vivo. Our results showed that 1.0 mu g/ml LPS induced a significant activation of astrocyte, shown as the marked increase in the glial fibrillary acidic protein (GFAP) expression, the cell viability and the number of 5-bromo-2'-deoxyuridine (BrdU)-positive living cells. Pretreatment with HN (5, 10, 20 mu M) led to a significant inhibition in astrocyte overactivation in a concentration dependent manner. We also found pretreatment with HN decreased the level of proinflammatory cytokines, interleukin (IL)-6, IL-1 beta and tumor necrosis factor alpha (TNF alpha) induced by LPS. Furthermore, we noticed HN couldn't completely reverse the above inflammatory injury. Our findings imply that HN partly antagonizes inflammation injury induced by LPS and the protective effect of HN on astrocyte is concentration-dependent.