title: Acetylbritannilactone Modulates MicroRNA-155-Mediated Inflammatory Response in Ischemic Cerebral Tissues.
abstract: Inflammatory responses play a critical role in ischemic brain injury. MicroRNA-155 (miR-155) induces the expression of inflammatory cytokines, and acetylbritannilactone (ABL) exerts potent antiinflammatory actions by inhibiting expression of inflammation-related genes. However, the functions of miR-155 and the actual relationship between ABL and miR-155 in ischemia-induced cerebral inflammation remain unclear. In this study, cerebral ischemia of wild-type (WT) and miR-155(-/-) mice was induced by permanent middle cerebral artery occlusion (MCAO). pAd-miR-155 was injected into the lateral cerebral ventricle 24 h before MCAO to induce miR-155 overexpression. MCAO mice and oxygen-glucose deprivation (OGD)-treated BV2 cells were used to examine the effects of ABL and miR-155 overexpression or deletion on the expression of proinflammatory cytokines. We demonstrated that ABL treatment significantly reduced neurological deficits and cerebral infarct volume by inhibiting tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) expression in ischemic cerebral tissue and OGD-treated BV2 cells. Mechanistic studies suggested that the observed decrease in TNF-α and IL-1β expression was attributable to the ABL-induced suppression of the expression of nuclear factor-kappa B (NF-κB) and Toll-like receptor 4 (TLR4). We further found that miR-155 promoted TNF-α and IL-1β expression by upregulating TLR4 and downregulating the expression of suppressor of cytokine signaling 1 (SOCS1) and myeloid differentiation primary response gene 88 (MyD88), while ABL exerted an inhibitory effect on miR-155-mediated gene expression. In conclusion, miR-155 mediates inflammatory responses in ischemic cerebral tissue by modulating TLR4/MyD88 and SOCS1 expression, and ABL exerts its antiinflammatory action by suppressing miR-155 expression, suggesting a novel miR-155-based therapy for ischemic stroke.
authors: Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, PR China.|Hebei Key Laboratory for Neurology, Shijiazhuang, Hebei, PR China.|Hebei Collaborative Innovation Center for Cardio-cerebrovascular Disease, Shijiazhuang, Hebei, PR China.
authors: Ya
authors: Y
authors: Wen
authors: Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, PR China.|Hebei Key Laboratory for Neurology, Shijiazhuang, Hebei, PR China.|Hebei Collaborative Innovation Center for Cardio-cerebrovascular Disease, Shijiazhuang, Hebei, PR China.
authors: Xiangjian
authors: X
authors: Zhang
authors: Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, PR China.|Hebei Key Laboratory for Neurology, Shijiazhuang, Hebei, PR China.
authors: Lipeng
authors: L
authors: Dong
authors: Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, PR China.|Hebei Key Laboratory for Neurology, Shijiazhuang, Hebei, PR China.
authors: Jingru
authors: J
authors: Zhao
authors: Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, PR China.|Hebei Key Laboratory for Neurology, Shijiazhuang, Hebei, PR China.
authors: Cong
authors: C
authors: Zhang
authors: Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, PR China.|Hebei Key Laboratory for Neurology, Shijiazhuang, Hebei, PR China.|Hebei Collaborative Innovation Center for Cardio-cerebrovascular Disease, Shijiazhuang, Hebei, PR China.
authors: Chunhua
authors: C
authors: Zhu
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D002460:Cell Line; D004195:Disease Models, Animal; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000187:drug effects; D007249:Inflammation / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D007783:Lactones / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics*; D017628:Microglia / Q000378:metabolism; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D015398:Signal Transduction; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism
chemical_list: D007783:Lactones; C524942:MIRN155 microRNA, human; D035683:MicroRNAs; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; C491590:Socs1 protein, mouse; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D051197:Toll-Like Receptor 4; C487680:acetylbritannilatone