scholarly journals LPS Primes Brain Responsiveness to High Mobility Group Box-1 Protein

2021 ◽  
Vol 14 (6) ◽  
pp. 558
Author(s):  
Verena Peek ◽  
Lois M. Harden ◽  
Jelena Damm ◽  
Ferial Aslani ◽  
Stephan Leisengang ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Area Postrema ◽  
High Mobility ◽  
High Mobility Group ◽  
Direct Access ◽  
Significant Release ◽  
Factor Α ◽  
Culture Supernatants

High mobility group box (HMGB)1 action contributes to late phases of sepsis, but the effects of increased endogenous plasma HMGB1 levels on brain cells during inflammation are unclear. Here, we aimed to further investigate the role of HMGB1 in the brain during septic-like lipopolysaccharide-induced inflammation in rats (LPS, 10 mg/kg, i.p.). HMGB-1 mRNA expression and release were measured in the periphery/brain by RT-PCR, immunohistochemistry and ELISA. In vitro experiments with disulfide-HMGB1 in primary neuro-glial cell cultures of the area postrema (AP), a circumventricular organ with a leaky blood–brain barrier and direct access to circulating mediators like HMGB1 and LPS, were performed to determine the direct influence of HMGB1 on this pivotal brain structure for immune-to-brain communication. Indeed, HMGB1 plasma levels stayed elevated after LPS injection. Immunohistochemistry of brains and AP cultures confirmed LPS-stimulated cytoplasmatic translocation of HMGB1 indicative of local HMGB1 release. Moreover, disulfide-HMGB1 stimulation induced nuclear factor (NF)-κB activation and a significant release of interleukin-6, but not tumor necrosis factor α, into AP culture supernatants. However, only a few AP cells directly responded to HMGB1 with increased intracellular calcium concentration. Interestingly, priming with LPS induced a seven-fold higher percentage of responsive cells to HMGB1. We conclude that, as a humoral and local mediator, HMGB1 enhances brain inflammatory responses, after LPS priming, linked to sustained sepsis symptoms.

scholarly journals Hepatocyte high-mobility group box 1 protects against steatosis and cellular stress during high fat diet feeding

2020 ◽  
Vol 26 (1) ◽  
Author(s):  
Minjie Lin ◽  
Jungke Long ◽  
Wenbo Li ◽  
Chenxuan Yang ◽  
Patricia Loughran ◽  
...  
Keyword(s):  
Er Stress ◽  
High Fat Diet ◽  
High Mobility ◽  
High Mobility Group ◽  
High Fat ◽  
Rapid Weight Gain ◽  
Nonalcoholic Fatty Liver ◽  
Primary Mouse

Abstract Background Circulating high-mobility group box 1 (HMGB1) plays important roles in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Intracellular HMGB1 is critical for the biology of hepatocytes. However, the intracellular role of HMGB1 in hepatocellular steatosis is unknown. Therefore, we aimed to investigate the role of hepatocyte-specific HMGB1 (HC-HMGB1) in development of hepatic steatosis. Methods Wild type (WT) C57BL/6 and HC-HMGB1−/− mice were fed high-fat diet (HFD) or low-fat diet (LFD) for up to 16 weeks. Results As expected, HMGB1 translocated from nuclear into cytoplasm and released into circulation after HFD treatment. HC-HMGB1 deficiency significantly reduced circulating HMGB1, suggesting that hepatocyte is a major source of circulating HMGB1 during NAFLD. Unexpectedly, HC-HMGB1 deficiency promoted rapid weight gain with enhanced hepatic fat deposition compared with WT at as early as 4 weeks after HFD treatment. Furthermore, there was no difference between WT and HC-HMGB1−/− mice in glucose tolerance, energy expenditure, liver damage or systemic inflammation. Interestingly, hepatic gene expression related to free fatty acid (FFA) β-oxidation was significantly down-regulated in HC-HMGB1−/− mice compared with WT, and endoplasmic reticulum (ER) stress markers were significantly higher in livers of HC-HMGB1−/− mice. In vitro experiments using primary mouse hepatocytes showed absence of HMGB1 increased FFA-induced intracellular lipid accumulation, accompanied by increased ER-stress, significant downregulation of FFA β-oxidation, and reduced oxidative phosphorylation. Conclusions Our findings suggest that hepatocyte HMGB1 protects against dysregulated lipid metabolism via maintenance of β-oxidation and prevention of ER stress. This represents a novel mechanism for HMGB1-regulation of hepatocellular steatosis, and suggests that stabilizing HMGB1 in hepatocytes may be effective strategies for prevention and treatment of NAFLD.

Role of High Mobility Group Box1 in Pathogenesis of Hepatitis C Virus induced Hepatocellular Carcinoma

2020 ◽  
Vol EJMM29 (4) ◽  
pp. 135-141
Author(s):  
Nouran E. Samra ◽  
Shahira El-Etreby ◽  
Rasha H. El-Mahdy ◽  
Samah S. El-Kazzaz ◽  
Nariman M. El-Nashar
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Response ◽  
Nuclear Dna ◽  
Inflammatory Responses ◽  
High Mobility ◽  
Dna Binding Protein ◽  
High Mobility Group ◽  
Over Expression ◽  
Different Types

Hepatocellular carcinoma "HCC" is a leading cause of cancer mortality worldwide. High-mobility group box 1 "HMGB1" is a nuclear DNA-binding protein which involved in DNA stability, programmed cell death, immune response and inflammatory responses in HCV and HCC. Its over expression was revealed in HCC and different types of human cancers.

The Role of High Mobility Group Box 1 Protein in Interleukin-18-Induced Myofibroblastic Transition of Valvular Interstitial Cells

Cardiology ◽  
2016 ◽  
Vol 135 (3) ◽  
pp. 168-178 ◽  
Author(s):  
Bo Wang ◽  
Guangxia Wei ◽  
Baoqing Liu ◽  
Xianming Zhou ◽  
Hua Xiao ◽  
...  
Keyword(s):  
Smooth Muscle Actin ◽  
Plasma Concentrations ◽  
High Mobility ◽  
High Mobility Group ◽  
Valvular Interstitial Cells ◽  
Interleukin 18 ◽  
Calcific Aortic Valve Disease ◽  
Vitro Model

Background: Increased levels of interleukin-18 (IL-18) and high mobility group box 1 protein (HMGB1) have been reported in patients with calcific aortic valve disease (CAVD). However, the role of IL-18 and HMGB1 in the modulation of the valvular interstitial cell (VIC) phenotype remains unclear. We hypothesized that HMGB1 mediates IL-18-induced myofibroblastic transition of VICs. Methods: The expression of IL-18, HMGB1 and α-smooth muscle actin (α-SMA) in human aortic valves was evaluated by immunohistochemical staining, real-time polymerase chain reaction and immunoblotting. Plasma concentrations of IL-18 and HMGB1 were measured using the ELISA kit. Cultured human aortic VICs were used as an in vitro model. Results: Immunohistochemistry and immunoblotting revealed increased levels of IL-18, HMGB1 and α-SMA in calcific valves. Circulating IL-18 and HMGB1 levels were also higher in CAVD patients. In vitro, IL-18 induced upregulation of HMGB1 and α-SMA in VICs. Moreover, IL-18 induced secretion of HMGB1 to the extracellular space and activation of nuclear factor kappa-B (NF-κB). Blockade of NF-κB abrogated the upregulation and release of HMGB1 induced by IL-18. Whereas HMGB1 inhibition attenuated the IL-18-induced expression of α-SMA, HMGB1 enhanced the effect of IL-18. Conclusions: We demonstrated for the first time that both tissue and plasma levels of IL-18 and HMGB1 were increased in patients with CAVD. Mechanically, HMGB1 mediated IL-18-induced VIC myofibroblastic transition.

High Mobility Group Box-1 Protein and Interleukin 33 Expression in Allergic Rhinitis

ORL ◽  
2022 ◽  
pp. 1-9
Author(s):  
Nongping Zhong ◽  
Qing Luo ◽  
Xiaoyan Huang ◽  
Jieqing Yu ◽  
Jing Ye ◽  
...  
Keyword(s):  
Allergic Rhinitis ◽  
Epithelial Cells ◽  
Nasal Mucosa ◽  
High Mobility ◽  
Normal Group ◽  
High Mobility Group ◽  
Hmgb1 Protein ◽  
Significant Difference

<b><i>Background:</i></b> Allergic rhinitis (AR) is characterized by an inflammatory reaction. High mobility group box 1 (HMGB1) protein and interleukin (IL)-33 are damage-associated molecular pattern molecules and have many characteristics similar to pro-inflammatory cytokines. However, the role of IL-33 and HMGB1 in AR remains unclear. The aim of this study is to explore the role of HMGB1 and IL-33 in AR. <b><i>Methods:</i></b> Twenty patients with AR (AR group) and 10 normal controls (normal group) were enrolled in this study. HMGB1 and IL-33 expression were analyzed by immunohistochemistry in epithelial cells of the inferior turbinate mucosa samples. Then, the human nasal mucosa epithelial cells (HNECs) were cultured in vitro, and the house dust mite allergen (Derp1) was used to stimulate the cells. Quantitative real-time PCR and ELISA assay were performed to detect HMGB1 and IL-33 expression in HNECs. <b><i>Results:</i></b> The expression of HMGB1 and IL-33 in the nasal mucosa was higher in the AR group than in the normal group, with a statistically significant difference (<i>p</i> &#x3c; 0.05). In HNECs of AR, the expression of both HMGB1 and IL-33 in stimulated groups was higher than that in non-stimulated groups. The differences were statistically significant (<i>p</i> &#x3c; 0.05). In addition, they increased gradually with the prolonging time and the concentration of the added Derp1. <b><i>Conclusions:</i></b> The expression of HMGB1 and IL-33 were both increased in AR. HMGB1 and IL-33 may have a close relationship in AR.

scholarly journals High Mobility Group Box 1 Protein Induction byMycobacterium BovisBCG

2007 ◽  
Vol 2007 ◽  
pp. 1-8 ◽  
Author(s):  
Péter Hofner ◽  
György Seprényi ◽  
András Miczák ◽  
Krisztina Buzás ◽  
Zsófia Gyulai ◽  
...  
Keyword(s):  
Mycobacterium Bovis ◽  
In Vitro Model ◽  
Nuclear Protein ◽  
High Mobility ◽  
High Mobility Group ◽  
Pathophysiological Role ◽  
Vitro Model

High mobility group box 1 protein (HMGB1), a nuclear protein, is a critical cytokine that mediates the response to infection, injury, and inflammation. The aim of our study was to elaborate a reliable in vitro model to investigate whetherMycobacterium bovisBCG is able to induce HMGB1 secretion from the monocytic U-937 cells. Western blot technique was applied for the detection of HMGB1 from supernatants of cells, following induction withMycobacterium bovisBCG. Densitometric analysis revealed higher concentrations of HMGB1 in cell supernatants stimulated with BCG than in the supernatants of the control, nonstimulated cells. Further quantitation of the secreted HMGB1 was performed by ELISA. The BCG strain resulted in a higher amount of secreted HMGB1 (450±44 ng/mL) than that of LPS (84±12 ng/mL) orStaphylococcus aureus(150±14 ng/mL). BCG and Phorbol−12-myristate−13acetate (PMA), added together, resulted in the highest HMGB1 secretion (645±125 ng/mL). The translocation of the HMGB1 towards the cytoplasm following infection of cells with BCG was demonstrated by immunofluorescence examinations. Conclusion: Our pilot experiments draw attention to the HMGB1 inducing ability ofMycobacterium bovis. Assesment of the pathophysiological role of this late cytokine in mycobacterial infections demands further in vitro and in vivo examinations.

scholarly journals Hepatocyte high-mobility group box 1 protects against steatosis and cellular stress during high fat diet feeding

2020 ◽  
Author(s):  
Minjie Lin ◽  
Jungke Long ◽  
Wenbo Li ◽  
Chenxuan Yang ◽  
Patricia Loughran ◽  
...  
Keyword(s):  
Er Stress ◽  
High Fat Diet ◽  
High Mobility ◽  
High Mobility Group ◽  
High Fat ◽  
Rapid Weight Gain ◽  
Nonalcoholic Fatty Liver ◽  
Primary Mouse

Abstract Background: Circulating high-mobility group box 1 (HMGB1) plays important roles in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Intracellular HMGB1 is critical for the biology of hepatocytes. However, the intracellular role of HMGB1 in hepatocellular steatosis is unknown. Therefore, we aimed to investigate the role of hepatocyte-specific HMGB1 (HC-HMGB1) in development of hepatic steatosis.Methods: Wild type (WT) C57BL/6 and HC-HMGB1-/- mice were fed high-fat diet (HFD) or low-fat diet (LFD) for up to 16 weeks.Results: As expected, HMGB1 translocated from nuclear into cytoplasm and released into circulation after HFD treatment. HC-HMGB1 deficiency significantly reduced circulating HMGB1, suggesting that hepatocyte is a major source of circulating HMGB1 during NAFLD. Unexpectedly, HC-HMGB1 deficiency promoted rapid weight gain with enhanced hepatic fat deposition compared with WT at as early as 4 weeks after HFD treatment. Furthermore, there was no difference between WT and HC-HMGB1-/- mice in glucose tolerance, energy expenditure, liver damage or systemic inflammation. Interestingly, hepatic gene expression related to free fatty acid (FFA) β-oxidation was significantly down-regulated in HC-HMGB1-/- mice compared with WT, and endoplasmic reticulum (ER) stress markers were significantly higher in livers of HC-HMGB1-/- mice. In vitro experiments using primary mouse hepatocytes showed absence of HMGB1 increased FFA-induced intracellular lipid accumulation, accompanied by increased ER-stress, significant downregulation of FFA β-oxidation, and reduced oxidative phosphorylation.Conclusions: Our findings suggest that hepatocyte HMGB1 protects against dysregulated lipid metabolism via maintenance of β-oxidation and prevention of ER stress. This represents a novel mechanism for HMGB1-regulation of hepatocellular steatosis, and suggests that stabilizing HMGB1 in hepatocytes may be effective strategies for prevention and treatment of NAFLD.

scholarly journals Hepatocyte high-mobility group box 1 protects against steatosis and cellular stress during high fat diet feeding

2020 ◽  
Author(s):  
Minjie Lin ◽  
Jungke Long ◽  
Wenbo Li ◽  
Chenxuan Yang ◽  
Patricia Loughran ◽  
...  
Keyword(s):  
Er Stress ◽  
High Fat Diet ◽  
High Mobility ◽  
High Mobility Group ◽  
High Fat ◽  
Rapid Weight Gain ◽  
Nonalcoholic Fatty Liver ◽  
Primary Mouse

Abstract Background: Circulating high-mobility group box 1 (HMGB1) plays important roles in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Intracellular HMGB1 is critical for the biology of hepatocytes. However, the intracellular role of HMGB1 in hepatocellular steatosis is unknown. Therefore, we aimed to investigate the role of hepatocyte-specific HMGB1 (HC-HMGB1) in development of hepatic steatosis. Methods: Wild type (WT) C57BL/6 and HC-HMGB1-/- mice were fed high-fat diet (HFD) or low-fat diet (LFD) for up to 16 weeks. Results: As expected, HMGB1 translocated from nuclear into cytoplasm and released into circulation after HFD treatment. HC-HMGB1 deficiency significantly reduced circulating HMGB1, suggesting that hepatocyte is a major source of circulating HMGB1 during NAFLD. Unexpectedly, HC-HMGB1 deficiency promoted rapid weight gain with enhanced hepatic fat deposition compared with WT at as early as 4 weeks after HFD treatment. Furthermore, there was no difference between WT and HC-HMGB1-/- mice in glucose tolerance, energy expenditure, liver damage or systemic inflammation. Interestingly, hepatic gene expression related to free fatty acid (FFA) β-oxidation was significantly down-regulated in HC-HMGB1-/- mice compared with WT, and endoplasmic reticulum (ER) stress markers were significantly higher in livers of HC-HMGB1-/- mice. In vitro experiments using primary mouse hepatocytes showed absence of HMGB1 increased FFA-induced intracellular lipid accumulation, accompanied by increased ER-stress, significant downregulation of FFA β-oxidation, and reduced oxidative phosphorylation. Conclusions: Our findings suggest that hepatocyte HMGB1 protects against dysregulated lipid metabolism via maintenance of β-oxidation and prevention of ER stress. This represents a novel mechanism for HMGB1-regulation of hepatocellular steatosis, and suggests that stabilizing HMGB1 in hepatocytes may be effective strategies for prevention and treatment of NAFLD.

scholarly journals MicroRNA-205-5p Targets HMGB1 to Suppress Inflammatory Responses during Lung Injury after Hip Fracture

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Xiaojie Yu ◽  
Xiaobin Chen ◽  
Tiansheng Sun
Keyword(s):  
Hip Fracture ◽  
Lung Injury ◽  
Inflammatory Responses ◽  
High Mobility ◽  
Alveolar Epithelial Cells ◽  
Luciferase Reporter ◽  
Serum Samples

Hip fracture is the most common type of injury in elderly people and is associated with a high incidence of complications and risk of mortality. In these patients, subsequent pulmonary infection can contribute to the development of an acute lung injury, a consequence of the systemic inflammatory response induced by hip fracture. Although the crucial role of microRNAs (miRNAs) in inflammatory responses has been established, the functions of miRNAs in the inflammatory responses associated with lung injury after hip fracture remain poorly understood. In this study, we explored the potential role of miR-205-5p in lung injury after hip fracture in an in vivo hip fracture model and in vitro cultures of human pulmonary alveolar epithelial cells (HPAEpiC). An analysis of clinical serum samples revealed increased levels of miR-205-5p and high mobility group box 1 (HMGB1) after hip fracture. A bioinformatics analysis and dual-luciferase reporter assay identified HMGB1 as a potential target of miR-205-5p. The overexpression of miR-205-5p clearly reduced the expression of HMGB1 and inhibited NF-κB signaling, apoptosis, and proinflammatory cytokine production while enabling continued cell proliferation. Our results demonstrate that the upregulation of miR-205-5p suppresses inflammatory responses and promotes cell viability and proliferation by selectively targeting HMGB1 in the context of lung injury after hip fracture. Therefore, miR-205-5p may be an alternative target of therapeutic strategies for lung injury after hip fracture.

High Mobility Group Box-1 (HMGB1): A Potential Target in Therapeutics

2019 ◽  
Vol 20 (14) ◽  
pp. 1474-1485 ◽  
Author(s):  
Eyaldeva C. Vijayakumar ◽  
Lokesh Kumar Bhatt ◽  
Kedar S. Prabhavalkar
Keyword(s):  
Myocardial Infarction ◽  
Vagus Nerve Stimulation ◽  
Nuclear Protein ◽  
Therapeutic Potential ◽  
High Mobility ◽  
Dna Binding Protein ◽  
High Mobility Group ◽  
Eukaryotic Cells ◽  
Hmgb1 Protein

High mobility group box-1 (HMGB1) mainly belongs to the non-histone DNA-binding protein. It has been studied as a nuclear protein that is present in eukaryotic cells. From the HMG family, HMGB1 protein has been focused particularly for its pivotal role in several pathologies. HMGB-1 is considered as an essential facilitator in diseases such as sepsis, collagen disease, atherosclerosis, cancers, arthritis, acute lung injury, epilepsy, myocardial infarction, and local and systemic inflammation. Modulation of HMGB1 levels in the human body provides a way in the management of these diseases. Various strategies, such as HMGB1-receptor antagonists, inhibitors of its signalling pathway, antibodies, RNA inhibitors, vagus nerve stimulation etc. have been used to inhibit expression, release or activity of HMGB1. This review encompasses the role of HMGB1 in various pathologies and discusses its therapeutic potential in these pathologies.

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