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KMID : 0892920130220040301
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Experimental Neurobiology
2013 Volume.22 No. 4 p.301 ~ p.307
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HMGB1-Binding Heptamer Confers Anti-Inflammatory Effects in Primary Microglia Culture
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Kim Il-Doo
Lee Ja-Kyeong
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Abstract
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High mobility group box 1 (HMGB1) is an endogenous danger signal molecule. In the postischemic brain, HMGB1 is massively released during NMDA-induced acute damage and triggers inflammatory processes. In a previous study, we demonstrated that intranasally delivered HMGB1 binding heptamer peptide (HBHP; HMSKPVQ) affords robust neuroprotective effects in the ischemic brain after middle cerebral artery occlusion (MCAO, 60 minutes). In the present study, we investigated HBHP-induced anti-inflammatory effects on microglia activation. In LPS-treated primary microglia culture, HMGB1 was rapidly released and accumulated in culture media. Furthermore, LPS-conditioned media collected from primary microglia cultures (LCM) activated naive microglia and markedly induced NO and proinflammatory cytokines. However, the suppression of HMGB1 by siRNA-HMGB1, HMGB1 A box, or anti-HMGB1 antibody significantly attenuated LCM-induced microglial activation, suggesting that HMGB1 plays a critical role in this process. A pull-down assay using biotin-labeled HBHP showed that HBHP binds directly to HMGB1 (more specifically to HMGB1 A box) in LCM. In addition, HBHP consistently inhibited LCM-induced microglial activation and suppressed the inductions of iNOS and proinflammatory cytokines. Together these results suggest that HBHP confers anti-inflammatory effects in activated microglia cultures by forming a complex with HMGB1.
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KEYWORD
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HMGB1, HBHP, inflammation, microglia
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