HMGB1 aggravates lipopolysaccharide-induced acute lung injury through suppressing the activity and function of Tregs

Li, Ruiting; Zhang, Jiancheng; Pan, Shangwen; Yuan, Yin; Qi, Hong; Shu, Huaqing; Hu, Yingying; Ren, Lehao; Jiang, Yongxiang; Yuan, Shiying

doi:10.1016/j.cellimm.2020.104192

Cited by 9 publications

(7 citation statements)

References 35 publications

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“… 25 , 38 , 39 In addition, recombinant HMGB1 can aggravate LPS-induced ALI, while anti-HMGB1 can significantly reduce the inflammatory response in this model. 40 Our data also demonstrate that the expression of HMGB1 is significantly up-regulated after LPS stimulation, whereas this elevation is inhibited by CAP, indicating that CAP may function as an HMGB1 inhibitor. Consistent with current results, our previous study also found CAP can protect against acetaminophen-induced acute liver injury by inhibiting HMGB1 expression.…”

Section: Discussionsupporting

confidence: 67%

Capsaicin Protects Against Lipopolysaccharide-Induced Acute Lung Injury Through the HMGB1/NF-κB and PI3K/AKT/mTOR Pathways

Chen

Zhan

et al. 2021

JIR

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Capsaicin (8-methyl-N-geranyl-6-nonamide; CAP) is an alkaloid isolated from chili peppers, which has complex pharmacological properties, including beneficial effects against various diseases. The aim of this study was to investigate the role of CAP in lipopolysaccharide (LPS)-induced acute lung injury (ALI), and the possible underlying mechanisms. Materials and Methods: ALI was induced by intranasal administration of LPS (0.5 mg/ kg), and CAP (1 mg/kg) injected intraperitoneally 3 days before exposure to LPS. Then, the histopathological changes were evaluated by hematoxylin and eosin staining. Enzyme-linked immunosorbent assay and qPCR were used to detect pro-inflammatory cytokines in serum and lung tissue. The expressions of HMGB1/NF-κB, PI3K/AKT/mTOR signaling pathways and apoptosis-associated molecules were determined by Western blot and/or qPCR. In addition, the lung cell apoptosis was analyzed by TUNEL staining, and the expression and location of cleaved caspase-3 were detected by immunofluorescence analysis. Results: CAP pretreatment significantly protected mice from LPS-induced ALI, with reduced lung wet/dry weight ratio, lung histological damage, myeloperoxidase (MPO) activity, malondialdehyde (MDA) content and pro-inflammatory cytokine levels, and significant increased superoxide dismutase (SOD) activity. In addition, CAP pretreatment significantly inhibited the high-mobility group protein B1 (HMGB1) expression, nuclear factor-kappa B (NF-κB) activation, and the PI3K/AKT/mTOR signaling pathway. Furthermore, mice pre-treated with CAP exhibited reduced apoptosis of lung tissues, with associated down-regulation of caspase-3, cleaved caspase-3, and BAX expression, and up-regulation of BCL-2. Conclusion: Our data demonstrate that CAP can protect against LPS-induced ALI by inhibiting oxidative stress, inflammatory responses and apoptosis through down-regulation of the HMGB1/NF-κB and PI3K/AKT/mTOR pathways.

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Section: Discussionsupporting

confidence: 67%

Capsaicin Protects Against Lipopolysaccharide-Induced Acute Lung Injury Through the HMGB1/NF-κB and PI3K/AKT/mTOR Pathways

Chen

Zhan

et al. 2021

JIR

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“…Considering T cell differentiation, once stimulated by pathogens or inflammatory cytokines, macrophages would release HMGB1. This protein can not only act on macrophage itself and prevent its assistance in Treg differentiation, but also directly impair Treg induction [ 101 , 111 ]. Moreover, recent study has found a much higher IL-17 level than Foxp3, revealing a serious imbalance between Th17 and Treg [ 39 , 112 , 113 ].…”

Section: Discussionmentioning

confidence: 99%

Regulatory T cell and macrophage crosstalk in acute lung injury: future perspectives

Guan

Zhou

et al. 2023

Cell Death Discov.

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Acute lung injury (ALI) describes the injury to endothelial cells in the lungs and associated vessels due to various factors. Furthermore, ALI accompanied by inflammation and thrombosis has been reported as a common complication of SARS-COV-2 infection. It is widely accepted that inflammation and the cytokine storm are main causes of ALI. Two classical anti-inflammatory cell types, regulatory T cells (Tregs) and M2 macrophages, are theoretically capable of resisting uncontrolled inflammation. Recent studies have indicated possible crosstalk between Tregs and macrophages involving their mutual activation. In this review, we discuss the current findings related to ALI pathogenesis and the role of Tregs and macrophages. In particular, we review the molecular mechanisms underlying the crosstalk between Tregs and macrophages in ALI pathogenesis. Understanding the role of Tregs and macrophages will provide the potential targets for treating ALI.

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“…HMGB1 protein binds to influenza virus nucleoprotein (NP) in nucleus and affects viral replication by maintaining viral polymerase activity [ 37 ]. It also inhibits the activity and function of immune cells and exacerbates LPS-induced acute lung injury (ALI) [ 38 ]. These results suggest that HMGB1, whether in cytoplasm or in the nucleus, can directly or indirectly regulate the progression of infection by pathogens.…”

Section: Discussionmentioning

confidence: 99%

Extracellular HMGB1 as Inflammatory Mediator in the Progression of Mycoplasma Gallisepticum Infection

Wang

et al. 2022

Cells

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High-mobility group box 1 (HMGB1), a member of damage-associated molecular patterns (DAMPs), is involved in the immune regulation of several infectious diseases. Mycoplasma gallisepticum (MG) infection is proved to cause an abnormal immune response, but the role of HMGB1 in MG-induced chronic respiratory disease (CRD) is unclear. In this study, we found that HMGB1 was released from the nucleus to the extracellular in macrophages upon infection with MG. Extracellular HMGB1 bound to TLR2 activating the NF-κB pathway triggering a severe inflammatory storm and promoting the progression of MG infection. More importantly, TLR4 could be activated by HMGB1 to trigger immune disorders after TLR2 was silenced. This disease process could be interrupted by ethyl pyruvate (EP) inhibition of HMGB1 release or glycyrrhizic acid (GA). Furthermore, treatment of MG-infected chickens with GA significantly alleviated immune organ damage. In conclusion, we demonstrate that HMGB1 is secreted extracellularly to form an inflammatory environment upon MG infection, triggering a further cellular inflammatory storm in a positive feedback approach. Blocking MG-induced HMGB1 release or suppression downstream of the HMGB1-TLR2/TLR4 axis may be a promising novel strategy for the treatment of CRD. Furthermore, this study may provide a theoretical reference for understanding non-LPS-activated TLR4 events.

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HMGB1 aggravates lipopolysaccharide-induced acute lung injury through suppressing the activity and function of Tregs

Cited by 9 publications

References 35 publications

Capsaicin Protects Against Lipopolysaccharide-Induced Acute Lung Injury Through the HMGB1/NF-κB and PI3K/AKT/mTOR Pathways

Capsaicin Protects Against Lipopolysaccharide-Induced Acute Lung Injury Through the HMGB1/NF-κB and PI3K/AKT/mTOR Pathways

Regulatory T cell and macrophage crosstalk in acute lung injury: future perspectives

Extracellular HMGB1 as Inflammatory Mediator in the Progression of Mycoplasma Gallisepticum Infection

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