HMGB1 functions

HMGB1 protein

HMGB1 in inflammatory response
HMGBl is an important inflammatory mediator that promotes inflammatory cell activation and stimulates the production and secretion of proinflammatory cytokines. HMGBl stimulates mononuclear cells to increase their adhesion, secrete more cytokines and proinflammatory mediators to stimulate neutrophils to increase their ability to migrate and adhere to the characteristics of dendritic cells to induce maturation, increase its surface marker expression and inflammation The expression of ICAM – 1 and VCAM – 1 on the surface of vascular endothelial cells increased the adhesion of endothelial cells to inflammatory cells. Stimulating the release of TNF-a, II, -8 and MCP-1 by vascular endothelial cells enhances the local inflammatory environment. Studies have shown that recombinant HMGBl and anti-CD3 monoclonal antibodies were added during human primary T lymphocyte culture. The results showed that HMGBl was the proliferative signal of activated T cells stimulated by suboptimal CD3 monoclonal antibody. The concentration of 0.25 ~ lmg · mLl of HMGBl on T cell proliferation stimulated with the dose gradually increased. It is concluded that HMGBl can act as a sign of activation T cells, mediate adaptive immune response.

HMGB1 in autoimmune diseases

Anti-HMGBl antibodies can be detected in sera from patients with rheumatoid arthritis (RA) and overexpression of HMGBl in synovial samples of RA patients. The recombinant HMGBl purified protein was injected into the column NMRI and the CBl7 germline of the mouse joint cavity, and 80% of the mice showed mild to moderate synovitis. And arthritis symptoms for at least 28 days. The above animal experiments confirmed that direct injection of HMGBl in the joint cavity induced arthritis. The clinical symptoms (mean arthritis score, somaticia) and histological changes (IL – 1p expression) were observed after 16 weeks of treatment of immuno – arthritis (CIA) model rats and mice with polyclonal anti – HMGBI antibody And articular cartilage destruction) and other aspects have significantly improved [. Overexpression of HMGBl was detected in dermis and epidermis of skin lupus erythematosus patients. Skeletal gland in patients with Sjogren’s syndrome also found an increase in HMGBl. Recently, Watanabe T et al. Have shown that HMGBl is elevated in aqueous humor and stimulates bone marrow-derived macrophages to produce TNF-a in experimental studies of experimental autoimmune uveitis (EAU) in Lewis rats. Angular inflammatory cells in the ocular tissue express HMGBl and its receptor RAGE. It is shown that HMGBl promotes and amplifies the inflammatory response of ocular tissue in EAU.

HMGB1 in tumor

HMGBl is a DNA-binding protein that plays an important role in transcription and may cause tumorigenesis when transcription occurs in certain genes. Studies have shown that in the course of tumor a large number of cell necrosis, to the surrounding release HMGBl. Resulting in a locally organized chronic inflammatory environment. Which leads to more normal cells necrosis or cancer, tumor cells long-term survival and gradually to the surrounding expansion. Kuniyasu et al observed 96 cases of gastric cancer specimens, found 65.0% RAGE expression was positive, 85.0% HMGBl positive expression. At the same time, it was found that the expression of RAGE was mainly focused on the edge of the tumor with invasiveness, which was closely related to the depth of tumor invasion and lymph node metastasis. HMGBl is overexpressed in a variety of tumor tissues, and its expression level is much higher than that of normal tissues. Studies have shown that. The coexpression of HMGBl and RAGE was positively correlated with the metastatic rate of prostate cancer and colon cancer and the mortality of patients. Given HMGBl or RAGE inhibitors, can significantly inhibit the proliferation and displacement of certain tumor cells. HMGBl in tumorigenesis, growth, diffusion process have a role, some scholars believe that HMGBI tumor diagnosis may be a characteristic indicator.


Also published on Medium.

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