Contribution of Toll‐like receptor/myeloid differentiation factor 88 signaling to murine liver regeneration†

Seki, Ekihiro; Tsutsui, Hiroko; Iimuro, Yuji; Naka, Tetsuji; Son, Gakuhei; Akira, Shizuo; Kishimoto, Tadamitsu; Nakanishi, Kenji; Fujimoto, Jiro

doi:10.1002/hep.20603

Cited by 155 publications

(179 citation statements)

References 48 publications

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“…This new molecular evidence and the additional role for the MyD88 adaptor in immediate early gene expression, is supported by published studies showing impaired immediate early gene expression and impaired tissue regeneration, in MyD88 À / À mice, following partial hepatectomy. 27 The combination of these published reports and our current results implicate the MyD88 pathway in immediate early gene expression. Therefore, efforts to develop specific MyD88-based pathway treatments will have to be directed at targets further downstream of this adaptor, and the signals that mediate immediate early gene expression.…”

Section: Discussionsupporting

confidence: 78%

A New Role for Downstream Toll-like Receptor Signaling in Mediating Immediate Early Gene Expression during Focal Cerebral Ischemia

Famakin

Mou

Johnson

et al. 2013

J Cereb Blood Flow Metab

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To better understand the role of downstream Toll-like receptor (TLR) signaling during acute cerebral ischemia, we performed cDNA microarrays, on brain RNA, and cytokine arrays, on serum, from wild type (WT), MyD88 À / À and TRIF-mutant mice, at baseline and following permanent middle cerebral artery occlusion (pMCAO). The acute stress response pathway was among the top pathways identified by Ingenuity Pathway Analysis of microarray data. We used real-time polymerase chain reaction to confirm the expression of four immediate early genes; EGR1, EGR2, ARC, Nurr77, in this pathway, and insulin degrading enzyme (IDE). Compared to WT, baseline immediate early gene expression was increased up to10-fold in MyD88 À / À and TRIF-mutant mice. However, following pMCAO, immediate early gene expression remained unchanged, from this elevated baseline in these mice, but increased up to 12-fold in WT. Furthermore, expression of IDE, which also degrades b-amyloid, decreased significantly only in TRIF-mutant mice. Finally, sE-Selectin, sICAM, sVCAM-1, and MMP-9 levels were significantly decreased only in MyD88 À / À compared with WT mice. We thus report a new role for downstream TLR signaling in immediate early gene expression during acute cerebral ischemia. We also show that the TRIF pathway regulates IDE expression; a major enzyme that clears b-amyloid from the brain.

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Section: Discussionsupporting

confidence: 78%

A New Role for Downstream Toll-like Receptor Signaling in Mediating Immediate Early Gene Expression during Focal Cerebral Ischemia

Famakin

Mou

Johnson

et al. 2013

J Cereb Blood Flow Metab

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show abstract

“…The TLR4-mediated MyD88-dependent signaling pathway is essential for NF-κB activation (30). MyD88 recruitment to the toll-interleukin receptor domain of TLR4 activates NF-κB, which is involved in cerebral ischemia/reperfusion injury (31,32).…”

Section: Discussionmentioning

confidence: 99%

Protective role of isoflurane pretreatment in rats with focal cerebral ischemia and the underlying molecular mechanism

Xiao

Ren

Yang

et al. 2012

Molecular Medicine Reports

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Abstract. Inflammation and immunity are important in the pathogenesis of cerebral ischemia. Toll-like receptor 4 (TLR4) is involved in the inflammatory responses of injured brain tissues. Emerging studies have focused on the effect of isoflurane (ISO) pretreatment on cerebral ischemia, however, the association between ISO pretreatment and TLR4 during cerebral ischemia remains to be elucidated. In the present study, the protective role of ISO pretreatment in rats with focal cerebral ischemia reperfusion was investigated and the molecular mechanism was discussed. Using a middle cerebral artery occlusion (MCAO) model, triphenyltetrazolium chloride staining was utilized to measure the infarct volume and brain edema and immunofluorescence staining was used to detect the MCAO-induced TLR4 expression and localization. Western blot analyses were conducted to quantify the protein expression levels of TLR4, myeloid differentiation primary response 88 (MyD88) and nuclear factor (NF)-κB in ischemic brain tissue at different time points. The results demonstrated that, following ISO pretreatment, the neurological deficits, brain edema and cerebral infarct size caused by ischemia/reperfusion were attenuated. The astrocyte and microglial activation in the brain tissue was decreased. In addition, the expression levels of TLR4, MyD88 and NF-κB were decreased. The present study indicated that ISO pretreatment may protect the brain from ischemic damage by downregulating the expression levels of TLR4, MyD88 and NF-κB.

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“…For immunohistochemical study of the p65 NF-B subunit, liver sections were incubated with goat anti-p65 antibody (Santa Cruz Biotechnology, Santa Cruz, CA) as previously described. 18 All procedures were approved by the Investigation and Ethics Committee and Institutional Animal Care and Use Committee of the Columbia University.…”

Section: Methodsmentioning

confidence: 99%

Roles of AKT and sphingosine kinase in the antiapoptotic effects of bile duct ligation in mouse liver†

et al. 2005

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Contribution of Toll‐like receptor/myeloid differentiation factor 88 signaling to murine liver regeneration†

Cited by 155 publications

References 48 publications

A New Role for Downstream Toll-like Receptor Signaling in Mediating Immediate Early Gene Expression during Focal Cerebral Ischemia

A New Role for Downstream Toll-like Receptor Signaling in Mediating Immediate Early Gene Expression during Focal Cerebral Ischemia

Protective role of isoflurane pretreatment in rats with focal cerebral ischemia and the underlying molecular mechanism

Roles of AKT and sphingosine kinase in the antiapoptotic effects of bile duct ligation in mouse liver†

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