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HMGB1 and pyroptosis

Lei Hou, Zhongwei Yang, Zhankui Wang, Xiao Zhang, Yanhua Zhao, Hao Yang, Beijie Zheng, Weitian Tian, Shaocheng Wang, Zhengyu He, Xiangrui Wang
Our previous study showed that high levels of HMGB1 existed in rats following cardiopulmonary bypass (CPB)-induced acute lung injury (ALI) and neutralization of high-mobility group box 1(HMGB1) reduced CPB-induced ALI. However, the mechanism by which CPB increases HMGB1 secretion is unclear. Recent studies have shown that inflammasome-mediated cell pyroptosis promotes HMGB1 secretion. This study aimed to investigate the relationship between inflammasome-mediated pyroptosis and HMGB1 in CPB-related ALI. We employed oxygen-glucose deprivation (OGD)-induced alveolar macrophage (AM) NR8383 pyroptosis to measure HMGB1 secretion...
June 8, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
Linsong Chen, Yanfeng Zhao, Dengming Lai, Peng Zhang, Yang Yang, Yuehua Li, Ke Fei, Gening Jiang, Jie Fan
In response to infection, polymorphonuclear neutrophils (PMN) are recruited in the infectious sites, and employ three major strategies to fight against the microbes including phagocytosis, degranulation, and neutrophil extracellular traps (NETs). NETs are a meshwork of chromatin fibers mixed with granule-derived antimicrobial peptides and enzymes, which trap and kill the bacteria extracellularly. In this study, by using a mouse sepsis model, we identified a novel mechanism by which NETs induce macrophage (Mϕ) pyroptosis, a caspase-1-dependent regulated cell death...
May 22, 2018: Cell Death & Disease
Nathalia Pizato, Beatriz Christina Luzete, Larissa Fernanda Melo Vasconcelos Kiffer, Luís Henrique Corrêa, Igor de Oliveira Santos, José Antônio Fagundes Assumpção, Marina Kiyomi Ito, Kelly Grace Magalhães
The implication of inflammation in pathophysiology of several type of cancers has been under intense investigation. Omega-3 fatty acids can modulate inflammation and present anticancer effects, promoting cancer cell death. Pyroptosis is an inflammation related cell death and so far, the function of docosahexaenoic acid (DHA) in pyroptosis cell death has not been described. This study investigated the role of DHA in triggering pyroptosis activation in breast cancer cells. MDA-MB-231 breast cancer cells were supplemented with DHA and inflammation cell death was analyzed...
January 31, 2018: Scientific Reports
Xu-Yu Zhang, Xi Chen, Hu-Fei Zhang, Su Guan, Shi-Hong Wen, Wen-Qi Huang, Zi-Meng Liu
BACKGROUND: To date, mechanisms of sepsis-induced intestinal epithelial injury are not well known. P2X7 receptor (P2X7R) regulates pyroptosis of lymphocytes, and propofol is usually used for sedation in septic patients. AIMS: We aimed to determine the occurrence of enterocyte pyroptosis mediated by P2X7R and to explore the effects of propofol on pyroptosis and intestinal epithelial injury after lipopolysaccharide (LPS) challenge. METHODS: A novel regimen of LPS challenge was applied in vitro and in vivo...
January 2018: Digestive Diseases and Sciences
Matthew J G Eldridge, Julia Sanchez-Garrido, Gil Ferreira Hoben, Philippa J Goddard, Avinash R Shenoy
Caspase-1 activation by inflammasome signaling scaffolds initiates inflammation and antimicrobial responses. Caspase-1 proteolytically converts newly induced pro-interleukin 1 beta (IL-1β) into its mature form and directs its secretion, triggering pyroptosis and release of non-substrate alarmins such as interleukin 1 alpha (IL-1α) and HMGB1. While some caspase-1 substrates involved in these events are known, the identities and roles of non-proteolytic targets remain unknown. Here, we use unbiased proteomics to show that the UBE2L3 ubiquitin conjugase is an indirect target of caspase-1...
January 31, 2017: Cell Reports
Yi-Dan Liang, Wen-Jing Bai, Chen-Guang Li, Li-Hui Xu, Hong-Xia Wei, Hao Pan, Xian-Hui He, Dong-Yun Ouyang
Piperine is a phytochemical present in black pepper (Piper nigrum Linn) and other related herbs, possessing a wide array of pharmacological activities including anti-inflammatory effects. Previously, we demonstrated that piperine has therapeutic effects on bacterial sepsis in mice, but the underlying mechanism has not been fully elucidated. In this study, we aimed to investigate the influences of piperine on pyroptosis in murine macrophages. The results showed that piperine dose-dependently inhibited ATP-induced pyroptosis, thereby suppressing interleukin-1β (IL-1β) or high mobility group box-1 protein (HMGB1) release in LPS-primed bone marrow-derived macrophages and J774A...
2016: Frontiers in Pharmacology
Guillermo Mazzolini, Jan-Peter Sowa, Ali Canbay
The liver is constantly exposed to a host of injurious stimuli. This results in hepatocellular death mainly by apoptosis and necrosis, but also due to autophagy, necroptosis, pyroptosis and in some cases by an intricately balanced combination thereof. Overwhelming and continuous cell death in the liver leads to inflammation, fibrosis, cirrhosis, and eventually hepatocellular carcinoma. Although data from various disease models may suggest a specific (predominant) cell death mode for different aetiologies, the clinical reality is not as clear cut...
December 1, 2016: Clinical Science (1979-)
Jie Yang, Yanfeng Zhao, Peng Zhang, Yuehua Li, Yong Yang, Yang Yang, Junjie Zhu, Xiao Song, Gening Jiang, Jie Fan
Hemorrhagic shock (HS) often renders patients more susceptible to lung injury by priming for an exaggerated response to a second infectious stimulus. Acute lung injury (ALI) is a major component of multiple organ dysfunction syndrome following HS and regularly serves as a major cause of patient mortality. The lung vascular endothelium is an active organ that has a central role in the development of ALI through synthesizing and releasing of a number of inflammatory mediators. Cell pyroptosis is a caspase-1-dependent regulated cell death, which features rapid plasma membrane rupture and release of proinflammatory intracellular contents...
September 8, 2016: Cell Death & Disease
A Takasu, A Masui, M Hamada, T Imai, S Iwai, Y Yura
Molecules essential for the induction of immunogenic cell death (ICD) are called damage-associated molecular patterns (DAMPs). The effects of oncolytic herpes simplex virus type 1 (HSV-1) on the production of DAMPs were examined in squamous cell carcinoma (SCC) cells. The cytopathic effects of HSV-1 RH2 were observed in mouse SCCVII cells infected at a high multiplicity of infection (MOI), and the amounts of viable cells were decreased. After being infected with RH2, ATP and high mobility group box 1 (HMGB1) were released extracellulary, while calreticulin (CRT) translocated to the cell membrane...
April 2016: Cancer Gene Therapy
Dongdong Wu, Pinhua Pan, Xiaoli Su, Lemeng Zhang, Qingwu Qin, Hongyi Tan, Li Huang, Yuanyuan Li
Previously, we demonstrated that pyroptosis in alveolar macrophages (AMs) plays an essential role in lipopolysaccharide (LPS)-induced acute lung injury. However, the underlying mechanism remains largely unclear. Here, we show that the absence of interferon regulatory factor 1 (IRF-1) in genetic knock-out mice strongly abrogates pyroptosis in AMs and alleviates the LPS-induced lung injury and systemic inflammation. Our study demonstrates that IRF-1 contributes to caspase-1 activation and apoptosis-associated speck-like protein containing a caspase activation and recruitment domain pyroptosome formation in AMs and leads to downstream inflammatory cytokine release, including that of IL-1β, IL-18, and HMGB1...
September 2016: Shock
Qiu-Ru Lin, Chen-Guang Li, Qing-Bing Zha, Li-Hui Xu, Hao Pan, Gao-Xiang Zhao, Dong-Yun Ouyang, Xian-Hui He
Gossypol, a polyphenolic compound isolated from cottonseeds, has been reported to possess many pharmacological activities, but whether it can influence inflammasome activation remains unclear. In this study, we found that in mouse macrophages, gossypol induced cell death characterized by rapid membrane rupture and robust release of HMGB1 and pro-caspase-11 comparable to ATP treatment, suggesting an induction of pyroptotic cell death. Unlike ATP, gossypol induced much low levels of mature interleukin-1β (IL-1β) secretion from mouse peritoneal macrophages primed with LPS, although it caused pro-IL-1β release similar to that of ATP...
February 1, 2016: Toxicology and Applied Pharmacology
H N Stephenson, A Herzig, A Zychlinsky
Immune cell death is often observed in response to infection. There are three potential beneficial outcomes after host cell death: (1) the removal of an intracellular niche for microbes, (2) direct microbicidal activity of released components and (3) the propagation of an inflammatory response. Recent findings suggest that three forms of non-apoptotic regulated cell death, pyroptosis, necroptosis and NETosis, can impact on immunity to bacterial infection. However, it is challenging to design experiments that unequivocally prove the advantageous effects of regulated cell death on immunity...
February 2016: Current Opinion in Immunology
Huan Yang, Haichao Wang, Sangeeta S Chavan, Ulf Andersson
High mobility group box protein 1 (HMGB1) is an evolutionary ancient nuclear protein that exerts divergent biological tasks inside and outside of cells. The functions of HMGB1 depend on location, binding partners and redox states of the molecule. In the nucleus, HMGB1 organizes DNA and nucleosomes and regulates gene transcription. Upon cell activation or injury, nuclear HMGB1 can translocate to the cytoplasm, where it is involved in inflammasome activation and pyroptosis, as well as regulation of the autophagy/apoptosis balance...
October 27, 2015: Molecular Medicine
Dobrin Draganov, Sailesh Gopalakrishna-Pillai, Yun-Ru Chen, Neta Zuckerman, Sara Moeller, Carrie Wang, David Ann, Peter P Lee
Overexpression of P2X7 receptors correlates with tumor growth and metastasis. Yet, release of ATP is associated with immunogenic cancer cell death as well as inflammatory responses caused by necrotic cell death at sites of trauma or ischemia-reperfusion injury. Using an FDA-approved anti-parasitic agent Ivermectin as a prototype agent to allosterically modulate P2X4 receptors, we can switch the balance between the dual pro-survival and cytotoxic functions of purinergic signaling in breast cancer cells. This is mediated through augmented opening of the P2X4/P2X7-gated Pannexin-1 channels that drives a mixed apoptotic and necrotic mode of cell death associated with activation of caspase-1 and is consistent with pyroptosis...
November 10, 2015: Scientific Reports
Dong-Dong Wu, Pin-Hua Pan, Ben Liu, Xiao-Li Su, Le-Meng Zhang, Hong-Yi Tan, Zu Cao, Zuo-Ren Zhou, Hai-Tao Li, Hao-Si Li, Li Huang, Yuan-Yuan Li
BACKGROUND: Pyroptosis is the term for caspase-1-dependent cell death associated with pro-inflammatory cytokines. The role of alveolar macrophage (AM) pyroptosis in the pathogenesis of the acute lung injury and acute respiratory distress syndrome (ALI/ARDS) remains unclear. METHODS: C57BL/6 wild-type mice were assigned to sham, lipopolysaccharide (LPS) + vehicle, LPS + acetyl-tyrosyl-valyl- alanyl-aspartyl-chloromethylketone (Ac-YVAD-CMK) and LPS + Z-Asp-Glu-Val-Asp-fluoromethylketone groups...
October 5, 2015: Chinese Medical Journal
M Magna, D S Pisetsky
Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by the production of antinuclear antibodies (ANAs) in association with systemic inflammation and organ damage. In addition to genetic factors, a contribution of infection to disease induction has been proposed. In the pathogenesis of lupus, immune complexes of ANAs with nuclear antigens can form and both deposit in the tissue and stimulate cytokine production to intensify inflammation. As such, the extracellular release of nuclear antigens to form pathogenic immune complexes is an important step in the pathway to disease...
September 2015: Scandinavian Journal of Immunology
Yan Geng, Qiang Ma, Ya-Nan Liu, Na Peng, Fang-Fang Yuan, Xing-Gui Li, Ming Li, Ying-Song Wu, Bing-ling Li, Wei-bing Song, Wei Zhu, Wei-Wen Xu, Jie Fan, Lei Su
BACKGROUND & AIMS: Liver injury is a common complication of heat stroke (HS), and often constitutes a direct cause for patient death. The cellular and molecular mechanism underlying HS-induced liver injury remains unclear. Recent evidence indicates that inflammasome plays an important role in mediating sterile inflammation triggered by tissue damage. Using a rat HS model, we identified a novel mechanism by which inflammasome-dependent interleukin-1β (IL-1β) activation and hepatocyte pyroptosis mediate HS-induced liver injury...
September 2015: Journal of Hepatology
Yan Yu, Daolin Tang, Rui Kang
High mobility group box 1 (HMGB1) is a widely-expressed and highly-abundant protein that acts as an extracellular signal upon active secretion by immune cells or passive release by dead, dying, and injured cells. Both intracellular and extracellular HMGB1 play pivotal roles in regulation of the cellular response to stress. Targeting the translocation, release, and activity of HMGB1 can limit inflammation and reduce tissue damage during infection and sterile inflammation. Although the mechanisms contributing to HMGB1 biology are still under investigation, it appears that oxidative stress is a central regulator of HMGB1's translocation, release, and activity in inflammation and cell death (e...
2015: Frontiers in Physiology
João D Martins, Joana Liberal, Ana Silva, Isabel Ferreira, Bruno Miguel Neves, Maria Teresa Cruz
Inflammation is a defensive response of the organism to manage harmful stimuli sensed by innate immune cells. The signal alarm is triggered by the recognition of pathogen-associated molecular patterns, such as microbial components, or host-derived damage-associated molecular patterns (DAMPs), namely high-mobility group box 1 protein (HMGB1) and purine metabolites, through a set of highly conserved receptors in immune cells termed pattern recognition receptors. Among these receptors, membrane-associated toll-like receptors (TLRs) and cytosolic nucleotide binding and oligomerization domain (nod)-like receptors (NLRs) assume particular relevance in the inflammatory process...
April 2015: DNA and Cell Biology
D Demon, A Kuchmiy, A Fossoul, Q Zhu, T-D Kanneganti, M Lamkanfi
Ulcerative colitis and Crohn's disease are major inflammatory syndromes that affect millions of patients. Caspase-11 confers protection against Gram-negative enteropathogens, but its role during colitis is unknown. Here, we show that caspase-11 was constitutively expressed in the colon, and that caspase-11-deficient (caspase-11(-/-)) mice were hypersusceptible to dextran sodium sulfate (DSS)-induced colitis. Notably, pro-inflammatory Prevotella species were strongly reduced in the gut microbiota of caspase-11(-/-) mice...
November 2014: Mucosal Immunology
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