title: LPS-Primed Release of HMGB-1 from Cortical Astrocytes is Modulated Through PI3K/AKT Pathway.
abstract: Studies have shown that LPS-preconditioned tolerant state could protect against brain injury to subsequent challenges. We hypothesized astrocytes were directly involved in the readjustment to confer neuroprotective effects with LPS pretreatment. High-mobility group box 1(HMGB-1) from LPS-preconditioned astrocytes, presumably serving as a positive regulator, might contribute to the favorable preconditioned effects. Furthermore, a potential cellular pathway (PI3K/AKT pathway), has been proposed for the active regulation of LPS-primed reactive astrocytes to secrete HMGB-1. In the present study, we used a low concentration of LPS to directly prime the astrocytes in vitro, and the subsequent astrocytic reactions, including cytokine secretion, the expression of transcription factors, and the release of HMGB-1 were examined after the blockade of the PI3K pathway. The data showed that LPS preconditioning could reduce some capacity of astrocytes to subsequent challenge in vitro. PI3K/AKT pathway was partially involved in the modulation of the release HMGB-1 from reactive astrocytes. These findings offer direct evidence supporting the flexible roles of astrocytes in mediating LPS-primed neuroprotection, and highlight additional targets for future attempts to modify the protective effects of astrocytes through LPS preconditioning.
authors.affiliation: The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China.
authors.forename: Ze-Feng
authors.initials: ZF
authors.lastname: Xie
authors.affiliation: Department of Microbiology and Immunology, Shantou University Medical College, 22, Xinling Road, Shantou, Guangdong, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Xin
authors.affiliation: Department of Microbiology and Immunology, Shantou University Medical College, 22, Xinling Road, Shantou, Guangdong, China.
authors.forename: Yan-Xuan
authors.initials: YX
authors.lastname: Xu
authors.affiliation: Department of Microbiology and Immunology, Shantou University Medical College, 22, Xinling Road, Shantou, Guangdong, China. yunsu112001@yahoo.com.
authors.forename: Yun
authors.initials: Y
authors.lastname: Su
authors.affiliation: Department of Microbiology and Immunology, Shantou University Medical College, 22, Xinling Road, Shantou, Guangdong, China. ksli@stu.edu.cn.
authors.forename: Kang-Sheng
authors.initials: KS
authors.lastname: Li
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology*; D002867:Chromones / Q000494:pharmacology; D024243:HMGB1 Protein / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008810:Mice, Inbred C57BL; D009025:Morpholines / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D002867:Chromones; D024243:HMGB1 Protein; D015850:Interleukin-6; D008070:Lipopolysaccharides; D009025:Morpholines; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt
keywords: Astrocyte; HMGB-1; LPS preconditioning; PI3K/AKT pathway