BACKGROUND: @entity1990 ( @entity1990 ) is activated in response to @entity2806 leading to substantial @entity75 . In contrast, mild activation of @entity1990 by preconditioning with low dose exposure to lipopolysaccharide (LPS) prior to @entity2806 dramatically improves outcome by reprogramming the signaling response to injury. This suggests that @entity1990 signaling can be altered to induce an endogenously neuroprotective phenotype. However, the @entity1990 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 @entity2806 and confer the neuroprotective phenotype. METHODS: C57BL6 @entity19 were preconditioned with low dose LPS prior to transient @entity2500 ( @entity2500 ). Cortical tissue and blood were collected following @entity2500 . Microarray and qtPCR were performed to analyze gene expression associated with @entity1990 signaling. EMSA and DNA binding ELISA were used to evaluate NFkB and @entity14055 activity. Protein expression was determined using Western blot or ELISA. @entity5001 -/- and @entity31512 -/- @entity19 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 @entity63 while pro-inflammatory genes induced following @entity63 were present but not differentially modulated by LPS. Interestingly, although expression of pro-inflammatory genes was observed, there was decreased activity of NFkB p65 and increased presence of NFkB inhibitors, including @entity20216 , @entity70388 , and @entity1991 , in LPS-preconditioned @entity19 following @entity64 . In contrast, @entity14055 activity was enhanced in LPS-preconditioned @entity19 following @entity64 . @entity31512 and @entity5001 deficient @entity19 revealed that neuroprotection induced by LPS depends on @entity1990 signaling via @entity31512 , which activates @entity14055 , but does not depend on @entity5001 signaling. CONCLUSION: Our results characterize several critical mediators of the @entity1990 signaling events associated with neuroprotection. LPS preconditioning redirects @entity1990 signaling in response to @entity64 through suppression of NFkB activity, enhanced @entity14055 activity, and increased anti-inflammatory/type I IFN gene expression. Interestingly, this protective phenotype does not require the suppression of pro-inflammatory mediators. Furthermore, our results highlight a critical role for @entity31512 - @entity14055 signaling as the governing mechanism in the neuroprotective response to @entity64 .

LPS preconditioning redirects TLR signaling following @entity64 : XXXX - @entity14055 plays a seminal role in mediating tolerance to @entity63 .

@entity20216 :: ('16331(Tax:10090)', 'Gene') :: ['Ship1'] @entity1991 :: ('18033(Tax:10090)', 'Gene') :: ['p105'] @entity64 :: ('MESH:D020521', 'Disease') :: ['stroke'] @entity2806 :: ('MESH:D002545', 'Disease') :: ['cerebral ischemia'] @entity63 :: ('MESH:D007511', 'Disease') :: ['ischemia'] @entity75 :: ('MESH:D001927', 'Disease') :: ['brain damage'] @entity2500 :: ('MESH:D020244', 'Disease') :: ['middle cerebral artery occlusion', 'MCAO'] @entity19 :: ('10090', 'Species') :: ['mice'] @entity31512 :: ('225471(Tax:10090)', 'Gene') :: ['TRIF'] @entity70388 :: ('54473(Tax:10090)', 'Gene') :: ['Tollip'] @entity14055 :: ('54131(Tax:10090)', 'Gene') :: ['IRF3'] @entity5001 :: ('17874(Tax:10090)', 'Gene') :: ['MyD88'] @entity1990 :: ('21898(Tax:10090)', 'Gene') :: ['TLR4', 'Toll-like receptor 4']
@entity31512 :: (225471(Tax:10090),Gene) :: ['TRIF']
