Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành hóa học dành cho các bạn yêu hóa học tham khảo đề tài: LPS preconditioning redirects TLR signaling following stroke: TRIF-IRF3 plays a seminal role in mediating tolerance to ischemic injury | Vartanian et al. Journal of Neuroinflammation 2011 8 140 http content 8 1 140 JOURNAL OF NEUROINFLAMMATION RESEARCH Open Access LPS preconditioning redirects TLR signaling following stroke TRIF-IRF3 plays a seminal role in mediating tolerance to ischemic injury Keri B Vartanian Susan L Stevens Brenda J Marsh Rebecca Williams-Karnesky Nikola S Lessov and Mary P Stenzel-Poore Abstract Background Toll-like receptor 4 TLR4 is activated in response to cerebral ischemia leading to substantial brain damage. In contrast mild activation of TLR4 by preconditioning with low dose exposure to lipopolysaccharide LPS prior to cerebral ischemia dramatically improves outcome by reprogramming the signaling response to injury. This suggests that TLR4 signaling can be altered to induce an endogenously neuroprotective phenotype. However the TLR4 signaling events involved in this neuroprotective response are poorly understood. Here we define several molecular mediators of the primary signaling cascades induced by LPS preconditioning that give rise to the reprogrammed response to cerebral ischemia and confer the neuroprotective phenotype. Methods C57BL6 mice were preconditioned with low dose LPS prior to transient middle cerebral artery occlusion MCAO . Cortical tissue and blood were collected following MCAO. Microarray and qtPCR were performed to analyze gene expression associated with TLR4 signaling. EMSA and DNA binding ELISA were used to evaluate NFkB and IRF3 activity. Protein expression was determined using Western blot or ELISA. MyD88- - and TRIF- - mice were utilized to evaluate signaling in LPS preconditioning-induced neuroprotection. Results Gene expression analyses revealed that LPS preconditioning resulted in a marked upregulation of anti-inflammatory type I IFN-associated genes following ischemia while pro-inflammatory genes induced following ischemia were present but not differentially modulated by LPS. Interestingly although expression of .
