气候变化领域集成服务门户(CCPortal): HMGB1 released from nociceptors mediates inflammation

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DOI	10.1073/pnas.2102034118
	HMGB1 released from nociceptors mediates inflammation
	Yang H.; Zeng Q.; Silverman H.A.; Gunasekaran M.; George S.J.; Devarajan A.; Addorisio M.E.; Li J.; Tsaava T.; Shah V.; Billiar T.R.; Wang H.; Brines M.; Andersson U.; Pavlov V.A.; Chang E.H.; Chavan S.S.; Tracey K.J.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:33
英文摘要	Inflammation, the body's primary defensive response system to injury and infection, is triggered by molecular signatures of microbes and tissue injury. These molecules also stimulate specialized sensory neurons, termed nociceptors. Activation of nociceptors mediates inflammation through antidromic release of neuropeptides into infected or injured tissue, producing neurogenic inflammation. Because HMGB1 is an important inflammatory mediator that is synthesized by neurons, we reasoned nociceptor release of HMGB1 might be a component of the neuroinflammatory response. In support of this possibility, we show here that transgenic nociceptors expressing channelrhodopsin-2 (ChR2) directly release HMGB1 in response to light stimulation. Additionally, HMGB1 expression in neurons was silenced by crossing synapsin-Cre (Syn-Cre) mice with floxed HMGB1 mice (HMGB1f/f). When these mice undergo sciatic nerve injury to activate neurogenic inflammation, they are protected from the development of cutaneous inflammation and allodynia as compared to wild-type controls. Syn-Cre/HMGB1fl/fl mice subjected to experimental collagen antibody-induced arthritis, a disease model in which nociceptor-dependent inflammation plays a significant pathological role, are protected from the development of allodynia and joint inflammation. Thus, nociceptor HMGB1 is required to mediate pain and inflammation during sciatic nerve injury and collagen antibody-induced arthritis. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Arthritis; Cytokine; DAMP; HMGB1; Sciatic nerve injury
语种	英语
scopus关键词	channelrhodopsin; channelrhodopsin 2; CXCL1 chemokine; high mobility group B1 protein; interleukin 6; monoclonal antibody; monoclonal antibody 2G7; tumor necrosis factor; unclassified drug; antibody; collagen; cytokine; Hbp1 protein, rat; high mobility group B1 protein; HMGB1 protein, mouse; adult; allodynia; animal cell; animal experiment; animal model; animal tissue; Article; cartilage degeneration; collagen antibody-induced arthritis; controlled study; cytokine response; dermatitis; drug dose comparison; female; male; mechanical hyperalgesia; mouse; nervous system inflammation; neurogenic inflammation; neuropathic pain; nonhuman; optogenetics; pain receptor; pannus; paw withdrawal latency; photostimulation; polyarthritis; rat; sciatic nerve injury; sensory nerve cell; spinal ganglion; synovitis; thermal hyperalgesia; animal; arthritis; C57BL mouse; cell culture; cytology; gene expression regulation; genetics; immunology; metabolism; nerve cell; pain receptor; physiology; sciatic neuropathy; Sprague Dawley rat; transgenic mouse; Wistar rat; Animals; Antibodies; Arthritis; Cells, Cultured; Collagen; Cytokines; Female; Ganglia, Spinal; Gene Expression Regulation; HMGB1 Protein; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Neurons; Nociceptors; Optogenetics; Rats; Rats, Sprague-Dawley; Rats, Wistar; Sciatic Neuropathy
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/251057
作者单位	Laboratory of Biomedical Sciences, Institute of Bioelectronic Medicine, Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY 11030, United States; Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, United States; Institute of Molecular Medicine, Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY 11030, United States; Department of Women's and Children's Health, Karolinska Institute, Karolinska University Hospital, Stockholm, 17176, Sweden; The Elmezzi Graduate School of Molecular Medicine, Manhasset, NY 11030, United States; Donald and Barbara Zucker School of Medicine, Hofstra University, Hempstead, NY 11549, United States
推荐引用方式 GB/T 7714	Yang H.,Zeng Q.,Silverman H.A.,et al. HMGB1 released from nociceptors mediates inflammation[J],2021,118(33).
APA	Yang H..,Zeng Q..,Silverman H.A..,Gunasekaran M..,George S.J..,...&Tracey K.J..(2021).HMGB1 released from nociceptors mediates inflammation.Proceedings of the National Academy of Sciences of the United States of America,118(33).
MLA	Yang H.,et al."HMGB1 released from nociceptors mediates inflammation".Proceedings of the National Academy of Sciences of the United States of America 118.33(2021).