Yang, Huan, Zeng, Qiong, Silverman, Harold A, Gunasekaran, Manojkumar, George, Sam J, Devarajan, Alex, Addorisio, Meghan E, Li, Jianhua, Tsaava, Téa, Shah, Vivek, Billiar, Timothy R, Wang, Haichao, Brines, Michael, Andersson, Ulf, Pavlov, Valentin A, Chang, Eric H, Chavan, Sangeeta S, Tracey, Kevin J (August 2021) HMGB1 released from nociceptors mediates inflammation. Proceedings of the National Academy of Sciences of USA, 118 (33). e2102034118-e2102034118. ISSN 0027-8424
Abstract
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.
| Item Type: | Paper |
|---|---|
| Subjects: | diseases & disorders organism description > animal diseases & disorders > inflammation > cytokines organs, tissues, organelles, cell types and functions > tissues types and functions > ganglia diseases & disorders > inflammation organism description > animal > mammal organism description > animal > mammal > rodent > mouse neurobiology > neuroanatomy neurobiology organs, tissues, organelles, cell types and functions organism description > animal > mammal > rodent > rat organism description > animal > mammal > rodent > rat organism description > animal > mammal > rodent organs, tissues, organelles, cell types and functions > tissues types and functions |
| CSHL Authors: | |
| Communities: | CSHL labs > Tracey lab |
| SWORD Depositor: | CSHL Elements |
| Depositing User: | CSHL Elements |
| Date: | 17 August 2021 |
| Date Deposited: | 20 Aug 2021 14:52 |
| Last Modified: | 25 Jan 2024 21:13 |
| PMCID: | PMC8379951 |
| URI: | https://repository.cshl.edu/id/eprint/40329 |
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