Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành y học dành cho các bạn tham khảo đề tài: Endotoxin-activated microglia injure brain derived endothelial cells via NF- B, JAK-STAT and JNK stress kinase pathways. | Kacimi et al. Journal of Inflammation 2011 8 7 http content 8 1 7 JOURNAL OF INFLAMMATION RESEARCH Open Access Endotoxin-activated microglia injure brain derived endothelial cells via NF-cB JAK-STAT and JNK stress kinase pathways Rachid Kacimi 1 Rona G Giffard2 Midori A Yenari1 Abstract Background We previously showed that microglia damage blood brain barrier BBB components following ischemic brain insults but the underlying mechanism s is are not well known. Recent work has established the contribution of toll-like receptor 4 TLR4 activation to several brain pathologies including ischemia neurodegeneration and sepsis. The present study established the requirement of microglia for lipopolysaccharide LPS mediated endothelial cell death and explored pathways involved in this toxicity. LPS is a classic TLR4 agonist and is used here to model aspects of brain conditions where TLR4 stimulation occurs. Methods Results In monocultures LPS induced death in microglia but not brain derived endothelial cells EC . However LPS increased EC death when cocultured with microglia. LPS led to nitric oxide NO and inducible NO synthase iNOS induction in microglia but not in EC. Inhibiting microglial activation by blocking iNOS and other generators of NO or blocking reactive oxygen species ROS also prevented injury in these cocultures. To assess the signaling pathway s involved inhibitors of several downstream TLR-4 activated pathways were studied. Inhibitors of NF-kB JAK-STAT and JNK SAPK decreased microglial activation and prevented cell death although the effect of blocking JNK SAPK was rather modest. Inhibitors of PI3K ERK and p38 MAPK had no effect. Conclusions We show that LPS-activated microglia promote BBB disruption through injury to endothelial cells and the specific blockade of JAK-STAT NF-kB may prove to be especially useful anti-inflammatory strategies to confer cerebrovascular protection. Background Microglia are the brain s resident immune .
