HMGB1-binding heptamer suppresses the synergistic effect of HMGB1 and LPS by interacting directly with HMGB1

Neuroscience Letters
Il-Doo KimJa-Kyeong Lee

Abstract

High mobility group box 1 (HMGB1) is an endogenous danger signal molecule. In the postischemic brain, HMGB1 is massively released during acute damaging process and triggers inflammatory processes. Moreover, it has been reported HMGB1 augments the proinflammatory effect of LPS by direct interaction. In previous studies, the authors showed intranasally delivered a HMGB1 binding heptamer peptide (HBHP; HMSKPVQ) has robust neuroprotective effects in the ischemic brain after middle cerebral artery occlusion and that it exerts an anti-inflammatory effect. In the present study, the authors investigated whether HBHP suppresses the augmentation of the proinflammatory effect of LPS by HMGB1. In primary microglial cultures, low doses of LPS (5 ng/ml) and recombinant HMGB1 (rHMGB1, 20 ng/ml) synergistically activated microglial cells, and HMGB1-LPS binding was detected. In addition, synergistic NO accumulation along with direct HMGB1-LPS binding was also observed when primary microglial cultures were treated with LPS (5 ng/ml) and HMGB1 accumulated in NMDA-conditioned medium (NCM). Co-treatment of microglial cells with HBHP and LPS or rHMGB1 (NCM), or treatment with rHMGB1 or NCM and LPS after pre-incubating rHMGB1 (or NCM) with HBHP marke...Continue Reading

References

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Jan 28, 2014·Experimental Neurobiology·Il-Doo Kim, Ja-Kyeong Lee

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