HMGB1-Binding Heptamer Confers Anti-Inflammatory Effects in Primary Microglia Culture
Experimental Neurobiology
;
: 301-307, 2013.
Artigo
em Inglês
| WPRIM
| ID: wpr-84006
ABSTRACT
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.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Encéfalo
/
Citocinas
/
Microglia
/
Fármacos Neuroprotetores
/
Infarto da Artéria Cerebral Média
/
Meios de Cultura
/
Proteína HMGB1
/
Inflamação
Idioma:
Inglês
Revista:
Experimental Neurobiology
Ano de publicação:
2013
Tipo de documento:
Artigo
Similares
MEDLINE
...
LILACS
LIS