A recent publication from Rudiito et al. in The Journal of the International Association of the Study of Pain demonstrated how high mobility group box 1 (HMGB1) and Toll-like receptor 4 (TLR4) are involved in arthritis-induced pain as confirmed by Chondrex, Inc.’s collagen-antibody induced arthritis (CAIA) models.
HMGB1, a pro-inflammatory cytokine, plays key roles in initiating inflammation and pain in a variety of acute and chronic inflammatory diseases. During inflammation, partly oxidized HMGB1 can activate TLR4 to increase cytokine production. A previous study reported that injecting lipopolysaccharide (a TLR4 ligand) into the spine theca induced hypersensitivity only in male mice even though both male and female mice express spinal TLR4. In this report, they used the CAIA model to investigate how blocking peripheral HMGB1 can attenuate pain-like behavior between male and female mice.
Both male and female CAIA mice revealed high HMGB1 mRNA levels in the ankle joints. Administering HMGB1 neutralizing antibodies failed to reduce arthritis severity in both male and female mice; however, it did significantly reverse CAIA-induced mechanical hypersensitivity in male mice. In addition, the differences in responses between sexes were evaluated by measuring cytokine levels (TNF, IL-6, CXCL1 and CXCL2) from cultured macrophages treated with HMGB1 and cytokine mRNA levels (TNF, IL-1b, IL-6, CCL2, CXCL1, and CXCL2) in paws which received HMGB1.
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1. R. Rudjito, N. M. Agalave, A. B. Farinotti, P. Lundbäck, T. A. Szabo-Pardi, T. J. Price, H. E. Harris, M. D. Burton, C. I. Svensson, Sex- and cell-dependent contribution of peripheral high mobility group box 1 and TLR4 in arthritis-induced pain. Pain 162(2):459-470, (2021)
In order to study the pathogenesis of HMGB1 and other pathogenic substances in CAIA mice, Chondrex Inc. provides arthritogenic monoclonal antibody cocktails, HMGB1, anti-HMGB1 antibodies, a HMGB1 detection kit, and Chemokine and Cytokine assay kits. Please refer to Chondrex, Inc.’s website for more information.
Collagen Antibody Induced Arthritis
Chemokine & Cytokine Detection ELISA Kits