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Severity of sepsisis is correlated with the elevation of serum high-mobility group box 1 in rats

Chinese Medical Journal 2009年第4期122卷 449-454页

作者： HOU Li-chao QIN Ming-zhe ZHENG Li-na LU Yan WANG Qiang PENG Dao-rong YU Xin-ping XIN Yu-chang JI Gen-lin XIONG Li-ze Department of Anesthesiology Xijing Hospital Fourth Military Medical University Xi'an Shaanxi 710032 China Center for Clinical Laboratory Medicine of People's LiberationArmy Department of Clinical Laboratory Xijing Hospital Fourth Military Medical University Xi'an Shaanxi 710032 China Department of Anesthesiology Tangdu Hospital Fourth Military Medical University Xi'an Shaanxi 710038 China

Background Sepsis is a leading cause of death in the intensive care units. The late inflammatory cytokine, high-mobility group box 1 （HMGB1）, plays a critical role in sepsis. In the present study, we investigated the association between the serum HMGB1 levels and the severity of organ injury in the lipopolysaccharide-induced sepsis in rats. Methods To produce an animal model of sepsis with different degree of organ injury, animals were treated with three different doses of lipopolysaccharide （4, 8 and 16 mg/kg）, and the animals in control group were treated with the same volume of the vehicle （saline）. The levels of serum HMGB1 were measured at 0, 2, 4, 8, 16, 24, 32 and 48 hours after lipopolysaccharide （LPS） or vehicle injection, meanwhile the biochemical and histopathological indicators for the severity of organ injury were assessed. Results The level of HMGB1 had a positive, high correlation with the abnormal changes of serum cardiac troponin I, alanine aminotransferase, aspartate aminotransferase, creatinine and blood urea nitrogen, as well as the pathologic scores of heart, lung, liver and kidney. Conclusions The level of serum HMGB1 is highly correlated with the severity of sepsis in rats, suggesting that HMGB1 could serve as a valuable adjunct in the diagnosis and management of sepsis.

关键词： lipopolysaccharide sepsis high-mobility group box 1 rat

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HMGB1 Inhibitor Effectively Alleviates Psoriasis-Like Lesions and Inflammatory Cytokines in K14-VEGF Transgenic Mice

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International Journal of Dermatology and Venereology 2023年第1期6卷 9-14页

作者： Li-Xin Fu Bin Yin Na Cao Sha Qin Xiao-Yu Lei Tao Chen Zai-Pei Guo Department of Dermatovenereology Chengdu Second People’s HospitalChengduSichuan 610041China Department of Dermatovenereology Chengdu Qingbaijiang Distinct People’s HospitalChengduSichuan 610300China Department of Dermatovenereology West China Hospital of Sichuan UniversityChengduSichuan 610041China

Objective:Anti-high-mobility group box 1(HMGB1)is involved in the pathogenesis of many inflammatory and autoimmune diseases,including psoriasis.The present study aimed to investigate the therapeutic effects of HMGB1 monoclonal antibody(mAb)in keratin 14(K14)-vascular endothelial growth factor(VEGF)transgenic homozygous mice.Methods:Twelve VEGF transgenic mice were randomly divided into two groups of six mice each:the anti-HMGB1 mAb group and the immune complex(IC)mAb group.The mice underwent intraperitoneal injection of anti-HMGB1 mAb or IC mAb once every 2 days for a total of three treatments.Compare the lesions on the ears of the mice and evaluate the severity of the lesions using the baseline and clinical scores on the last day of treatment.The changes in psoriasis-like lesions,cellular infiltration of T cells,dendritic cells,and neutrophils were detected by hematoxylin-eosin staining and immunohistochemistry.The mRNA expression of the inflammatory cytokines,including interleukin(IL)-6,tumor necrosis factor-α,interferon-γ,and IL-17 in the lesions were assessed by real-time quantitative polymerase chain reaction.The number ofγδT cells in the lesions of two groups were detected by flow cytometry.Thet test was used to compare their differences.Results:The anti-HMGB1 mAb effectively ameliorated the clinical skin lesions.The clinical scores in the anti-HMGB1 mAb group were lower than those in the IC mAb group(6.00±0.52vs.10.83±0.48,Pgroup were significantly lower than those in the IC mAb group(3.25±0.71vs.6.95±0.83,P=0.0033).The average epidermal thickness in the anti-HMGB1 mAb group was reduced by about 45%when compared with that in the IC mAb group(32.15±7.08vs.64.69±7.93,P=0.0054).Moreover,anti-HMGB1 mAb also decreased the number of infiltrating CD3+T cells,myeloperoxidase-positive neutrophils,and CD11c+dendritic cells.The ratio of ear skinγδT ce

关键词： high-mobility group box 1 inflammatory cytokines K14-VEGF transgenic mouse psoriasis

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Transcription and Secretion of Interleukin-1β and HMGB1 in Keratinocytes Exposed to Stimulations Mimicking Common Inflammatory Damages

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International Journal of Dermatology and Venereology 2023年第3期6卷 121-129页

作者： Xue-Cui Wei Yu-Jie Chen Fang-Yuan Long Shan-Shan Yu Song Xu Xu Chen School of Public Health Nanjing Medical UniversityNanjingJiangsu 211166China Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs Hospital for Skin Diseases(Institute of Dermatology)Chinese Academy of Medical Sciences&Peking Union Medical CollegeNanjingJiangsu 210042China Key Laboratory of Basic and Translational Research on Immune-Mediated Skin Diseases Hospital for Skin Diseases(Institute of Dermatology)Chinese Academy of Medical Sciences&Peking Union Medical CollegeNanjingJiangsu 210042China

Objective:Interleukin-1β(IL-1β)and high-mobility group box 1(HMGB1)are widely known damage-associated molecular patterns(DAMPs).However,their expression and secretion in different skin diseases,especially in inflammatory skin disorders,remain to be further elucidated.This study was performed to explore and compare the transcriptional and secretory levels of IL-1β and HMGB1 in keratinocytes under 3 types of stimulation:ultraviolet B(UVB)irradiation;co-stimulation by tumor necrosis factor-α(TNF-α)and interferon-γ(IFN-γ)(simulation of T helper 1 cell inflammatory challenge);and psoriasis-like stimulation by M5,a mixture of 5 proinflammatory cytokines.Methods:We used quantitative reverse-transcription polymerase chain reaction to determine the transcription levels of IL-1β and HMGB1.Western blotting and enzyme-linked immunosorbent assay were used to detect the secretion levels of IL-1β and HMGB1.The results were statistically analyzed by t test.Results:A rapid transcriptional and secretory response of IL-1β from keratinocytes occurred in all 3 types of stimulation mimicking common inflammatory environments(P1 was inhibited in all 3 types of stimulation(P1 after treatment with M5(P=0.196).Conclusion:IL-1β is a critical cytokine for the immunomodulatory functions of keratinocytes in inflammatory responses.In this study,keratinocytes restrained transcription of HMGB1 when the secretion of HMGB1 was induced in certain stimulations(eg,by UVB exposure or stimulation by TNF-α and IFN-γ).

关键词： damage-associated molecular patterns interleukin-1β high-mobility group box 1 keratinocytes inflammatory skin disorders

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The Anti-inflammatory Activity of HMGB1 A box is Enhanced When Fused with C-terminal Acidic Tail

The Anti-inflammatory Activity of HMGB1 A Box is Enhanced Wh...

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重庆市生物化学与分子生物学学术会议

作者： Wei Gong1,Yingru Zheng2,Fan Chao1,Yuan Li1,Zhizhen Xu1,Gang Huang1,Xiang Gao3,Song Li3,Fengtian He1 (1 Department of Biochemistry and Molecular Biology,College of Basic Medical Sciences,Third Military Medical University,Chongqing 400038,China 2 Department of Obstetrics and Gynecology, Research Institute of Surgery,Daping Hospital,Third Military Medical University,Chongqing 400042, China 3 Center for Pharmacogenetics,Department of Pharmaceutical Sciences,School of Pharmacy, University of Pittsburgh,Pittsburgh,PA 15261,USA)

HMGB1,composed of the A box,B box and C tail domains,is a critical proinflammatory cytokine involved in diverse inflammatory diseases.The B box mediates proinflammatory activity,while the A box alone acts as a specific antagonist of HMGB1.The C tail contributes to the spatial structure of A box and regulates HMGB1 DNA binding specificity.It is unknown whether the C tail can enhance the

关键词： high-mobility group box 1 A box C-terminal acidic tail Inflammation Fusion protein

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Combination BMSCs and Glycyrrhizin treatment of stroke inhibits the expression of HMGB1 and RAGE in diabetic rats

Combination BMSCs and Glycyrrhizin treatment of stroke inhib...

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华东六省一市第二十三次神经病学学术会议暨2016年浙江...

作者： Jienan Zhu Jinxia Hu Bin Liu Qiuchen Zhao Zunsheng Zhang Kun Zan Guiyun Cui Xinchun Ye Department of Neurology the Affiliated Hospital of Xuzhou Medical College Department of Geriatric Neurology Nanjing Brain HospitalAffiliated to Nanjing Medical University Department of Neurology Affiliated Drum Tower Hospital of Nanjing University Medical School

Our previous study indicated that bone marrow stromal cells(BMSCs) treatment exerted adverse effects after stroke in type 1 diabetic rats(T1DM),the possible mechanisms by which BMSCs treatment exacerbated blood-brain barrier(BBB) leakage and functional outcomes remain unclear.In this study,we investigated whether the highmobility group box 1(HMGB1)/receptor for advanced glycation endproducts(RAGE) axis signaling in contributed to the adverse effects in type 1 diabetic stroke caused by BMSCs treatment.Type 1 diabetes mellitus(T1 DM) rats were subjected to middle cerebral artery occlusion(MCAo) and 24 hours later were treated with:(1) phosphate-bufferedsaline;(2) BMSCs(3 × 106);(3) Gly(Glycyrrhizin,an HMGB1 inhibitor,4 mg/kg) and(4) BMSCs(3 × 106) + Gly(4 mg/kg) starting at 24 hours after MCAo and monitored for 14 days.Functional tests,immunostaining,and western blot were performed.BMSCs monotherapy of stroke in T1DM rats significandy increased HMGB1 and RAGE expression in the ischemic brain when compared to T1DM-MCAo control rats.However,BMSCs monotherapy exacerbated functional outcome.Gly monotherapy and combination of Gly and BMSCs treatment significantly improve functional outcomes and reduce the levels of HMGB1 and RAGE in the ischemic brain when compared to T1DM control or BMSCs monotherapy groups.The HMGB1/RAGE axis signaling may play a vital role in BMSCs treatment induced functional impairments after stroke in T1DM rats.Inhibition of the HMGB1/RAGE axis signaling pathway by Gly may attenuate the adverse effects induced by BMSCs treatment in T1DM-MCAo rats.

关键词： high-mobility group box 1 receptor for advanced glycation endproducts bone marrow stromal cells ischemic stroke type 1 diabetes mellitus

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