High mobility group box 1 mediates inflammatory response of astrocytes via cyclooxygenase 2/prostaglandin E2 signaling following spinal cord injury  

作　　者：Hong-Hua Song Tian-Cheng Song Ting Yang Chun-Shuai Sun Bing-Qiang He Hui Li Ying-Jie Wang Yu Li Hao Wu Yu-Ming Hu Yong-Jun Wang 

机构地区：[1]Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education,Co-innovation Center of Neuroregeneration,Nantong University,Nantong,Jiangsu Province,China [2]Center of Special Inspection,Affiliated Hospital of Nantong University,Nantong,Jiangsu Province,China [3]Department of Neurosurgery,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,Hubei Province,China [4]Department of Otolaryngology Head Neck Surgery,Affiliated Hospital of Nantong University,Nantong,Jiangsu Province,China [5]Department of Rehabilitation Medicine,Affiliated Hospital of Nantong University,Nantong,Jiangsu Province,China

出　　处：《Neural Regeneration Research》2021年第9期1848-1855,共8页中国神经再生研究（英文版）

基　　金：supported by the National Key Research and Development Program of China,No.2018YFC1105603(to YJunW);the National Natural Science Foundation of China,No.31871211(to YJunW);the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)(to YJunW);the China Postdoctoral Science Foundation,No.2020M681689(to YMH);the Basic Scientific Research Projects of Nantong of China,No.JC2018065(to HHS)。

摘　　要：High mobility group box 1(HMGB1) interacts with pattern-recognition receptors of immune cells to activate the inflammatory response. Astrocytes play a positive role in the inflammatory response of the central nervous system by expressing a broad range of patternrecognition receptors. However, the underlying relationship between HMGB1 and the inflammatory reaction of astrocytes remains unclear. In this study, we established rat models of spinal cord injury via laminectomy at the T8–10 level, and the injured spinal cord was subjected to transcriptome sequencing. Our results showed that the HMGB1/Toll-like receptor 4(TLR4) axis was involved in the activation of astrocyte inflammatory response through regulation of cyclooxygenase 2(COX2)/prostaglandin E2(PGE2) signaling. Both TLR4 and COX2 were distributed in astrocytes and showed elevated protein levels following spinal cord injury. Stimulation of primary astrocytes with recombinant HMGB1 showed that COX2 and microsomal PGE synthase(mPGES)-1, rather than COX1, mPGES-2, or cytosolic PGE synthase, were significantly upregulated. Accordingly, PGE2 production in astrocytes was remarkably increased in response to recombinant HMGB1 challenges. Pharmacologic blockade of TLR2/4 attenuated HMGB1-mediated activation of the COX2/PGE2 pathway. Interestingly, HMGB1 did not impact the production of tumor necrosis factor-α or interleukin-1β in astrocytes. Our results suggest that HMGB1 mediates the astrocyte inflammatory response through regulating the COX2/PGE2 signaling pathway. The study was approved by the Laboratory Animal Ethics Committee of Nantong University, China(approval No. 20181204-001) on December 4, 2018.

关 键 词：ASTROCYTES COX2 HMGB1 inflammation spinal cord injury 

分 类 号：R651.2[医药卫生—外科学]