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inflammasome, inflammation, ROS, lung

Yi Li, Haitao Li, Shuai Liu, Pinhua Pan, Xiaoli Su, Hongyi Tan, Dongdong Wu, Lemeng Zhang, Chao Song, Minhui Dai, Qian Li, Zhi Mao, Yuan Long, Yongbin Hu, Chengping Hu
Acute respiratory distress syndrome(ARDS)is a severe clinical disorder characterized by its acute onset, diffuse alveolar damage, intractable hypoxemia, and non-cardiogenic pulmonary edema. Acute lung injury(ALI) can trigger persistent lung inflammation and fibrosis through activation of the NLRP3 inflammasome and subsequent secretion of mature IL-1β, suggesting that the NLRP3 inflammasome is a potential therapeutic target for ALI, for which new therapeutic approaches are needed. Our present study aims to assess whether pirfenidone,with anti-fibrotic and anti-inflammatory properties, can improve LPS-induced inflammation and fibrosis by inhibiting NLRP3 inflammasome activation...
May 18, 2018: Molecular Immunology
Zhaohui Liu, Min Qu, Lili Yu, Panpan Song, Yulin Chang
The molecular mechanisms of acute lung injury (ALI) are closely associated with nucleotide-binding domains and leucine-rich repeat (NLR) pyrin domains containing 3 (NLRP3) inflammasome, in which alveolar macrophages (AMs) exert an essential function. Our study has been proved that artesunate (AS) inhibits ALI. Nevertheless, the inhibition actions of AS on activation of NLRP3 in renal ischemia-reperfusion (RIR)-mediated ALI remain to be further discussed. Male Sprague-Dawley rats were randomly assigned into four groups: sham + NS, sham + AS, RIR + NS, and RIR + AS...
May 5, 2018: Inflammation
Ying Lu, Ting Yu, Jingyao Liu, Lina Gu
BACKGROUND: A major feature of acute lung injury (ALI) is excessive inflammation in the lung. Vitexin is an active component from medicinal plants which has antioxidant and anti-inflammatory activities. Oxidative stress and inflammation play important roles in the pathophysiological processes in ALI. In the current study, we investigate the effect and potential mechanisms of Vitexin on lipopolysaccharide (LPS)-induced ALI. METHODS: ALI was induced by LPS intratracheal instillation in C57BL/6 wild-type mice and Nrf2 gene knocked down (Nrf2-/-) mice...
2018: PloS One
Wen-Cheng Chao, Chia-Liang Yen, Cheng-Yuan Hsieh, Ya-Fang Huang, Yau-Lin Tseng, Peter Andrija Nigrovic, Chi-Chang Shieh
Granulomatous inflammation causes severe tissue damage in mycobacterial infection while redox status was reported to be crucial in the granulomatous inflammation. Here, we used a NADPH oxidase 2 (NOX2)-deficient mice (Ncf1-/-) to investigate the role of leukocyte-produced reactive oxygen species (ROS) in mycobacterium-induced granulomatous inflammation. We found poorly controlled mycobacterial proliferation, significant body weight loss, and a high mortality rate after M. marinum infection in Ncf1-/- mice. Moreover, we noticed loose and neutrophilic granulomas and higher levels of interleukin (IL)-1β and neutrophil chemokines in Ncf1-/- mice when compared with those in wild type mice...
2017: PloS One
Vinicius Nunes Cordeiro Leal, Isabel Rugue Genov, Márcia C Mallozi, Dirceu Solé, Alessandra Pontillo
Considering its role in inflammation and recently described "alternative" roles in epithelial homeostasis and Th1/Th2 balance, we hypothesize that inflammasome genetics could contribute to the development of asthma. Selected functional polymorphisms in inflammasome genes are evaluated in a cohort of asthmatic children and their families. Gain-of-function NLRP1 variants rs11651270, rs12150220 and rs2670660 resulted significantly associated to asthma in trios (TDT) analysis; and rs11651270 and rs2670660 also with asthma severity and total IgE level in asthmatic children...
January 2018: Molecular Immunology
Huiyuan Zheng, Johan Högberg, Ulla Stenius
Silica exposure is a common risk factor for lung cancer. It has been claimed that key elements in cancer development are activation of inflammatory cells that indirectly induce DNA damage and proliferative stimuli in respiratory epithelial cells. We studied DNA damage induced by silica particles in respiratory epithelial cells and focused the role of the signaling enzyme autotaxin (ATX). A549 and 16HBE lung epithelial cells were exposed silica particles. Reactive oxidative species (ROS), NLRP3 inflammasome activation, ATX, ataxia telangiectasia mutated (ATM), and DNA damage (γH2AX, pCHK1, pCHK2, comet assay) were endpoints...
September 15, 2017: Carcinogenesis
Xiao Liang, Di Zhang, Wenjia Liu, Yingjie Yan, Fang Zhou, Weidong Wu, Zhen Yan
Inhaled zinc oxide nanoparticles (ZnO-NPs) induce lung inflammation associated with oxidative stress. The NLRP3 inflammasome plays a pivotal role in the development of lung inflammation. However, the underlying effects of the NLRP3 inflammasome on ZnO-NPs-induced inflammation remain obscure. In the present study, reactive oxygen species (ROS) generation, expression of NLRP3, caspase-1 p10, and cytokines release of interleukin (IL)-1β and IL-18 were determined after A549 cells were exposed to ZnO-NPs. The ROS scavenger N-acetyl-L-cysteine (NAC), nuclear factor kappa B (NF-κB inhibitor BAY11-7082, and NLRP3 inhibitor glibenclamide (GEL) were used to explore the mechanism of NLRP3 inflammasome activation-induced by ZnO-NPs...
October 2017: Toxicology and Industrial Health
Misato Tsugita, Nobuyuki Morimoto, Masafumi Nakayama
Silicon dioxide (SiO2 ) nanoparticles (NPs) and titanium dioxide (TiO2 ) NPs are the most widely used inorganic nanomaterials. Although the individual toxicities of SiO2 and TiO2 NPs have been extensively studied, the combined toxicity of these NPs is much less understood. In this study, we observed unexpected and drastic activation of the caspase-1 inflammasome and production of IL-1β in mouse bone marrow-derived macrophages stimulated simultaneously with SiO2 and TiO2 NPs at concentrations at which these NPs individually do not cause macrophage activation...
April 11, 2017: Particle and Fibre Toxicology
Qinmei Liu, Xinxin Ci, Zhongmei Wen, Liping Peng
Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a common clinical syndrome of diffuse lung inflammation with high mortality rates and limited therapeutic methods. Diosmetin, an active component from Chinese herbs, has long been noticed because of its antioxidant and anti-inflammatory activities. The aim of this study was to evaluate the effects of diosmetin on LPS-induced ALI model and unveil the possible mechanisms. Our results revealed that pretreatment with diosmetin effectively alleviated lung histopathological changes, which were further evaluated by lung injury scores...
March 1, 2018: Biomolecules & Therapeutics
Byeong Gon Kim, Pureun Haneul Lee, Sun Hye Lee, Moo Kyun Park, An Soo Jang
PURPOSE: Nanoparticles (NPs) may cause cell and tissue damage, leading to local and systemic inflammatory responses and adverse effects on health due to the inhalation of particulate matter. The inflammasome is a major regulator of inflammation through its activation of pro-caspase-1, which cleaves pro-interleukin-1β (pro-IL-1β) into its mature form and may induce acute and chronic immune responses to NPs. However, little is known about the response of the inflammasome to NP exposure via the airways in asthma...
May 2017: Allergy, Asthma & Immunology Research
Hongming Lv, Qinmei Liu, Zhongmei Wen, Haihua Feng, Xuming Deng, Xinxin Ci
Abundant natural flavonoids can induce nuclear factor-erythroid 2 related factor 2 (Nrf2) and/or AMP-activated protein kinase (AMPK) activation, which play crucial roles in the amelioration of various inflammation- and oxidative stress-induced diseases, including acute lung injury (ALI). Xanthohumol (Xn), a principal prenylflavonoid, possesses anti-inflammation and anti-oxidant activities. However, whether Xn could protect from LPS-induced ALI through inducing AMPK/Nrf2 activation and its downstream signals, are still poorly elucidated...
August 2017: Redox Biology
Tian Liu, Yong Zhou, Ping Li, Jia-Xi Duan, Yong-Ping Liu, Guo-Ying Sun, Li Wan, Liang Dong, Xiang Fang, Jian-Xin Jiang, Cha-Xiang Guan
Acute lung injury (ALI) is associated with high mortality and uncontrolled inflammation plays a critical role in ALI. TREM-1 is an amplifier of inflammatory response, and is involved in the pathogenesis of many infectious diseases. NLRP3 inflammasome is a member of NLRs family that contributes to ALI. However, the effect of TREM-1 on NLRP3 inflammasome and ALI is still unknown. This study aimed to determine the effect of TREM-1 modulation on LPS-induced ALI and activation of the NLRP3 inflammasome. We showed that LR12, a TREM-1 antagonist peptide, significantly improved survival of mice after lethal doses of LPS...
December 22, 2016: Scientific Reports
Tina M Sager, Michael Wolfarth, Stephen S Leonard, Anna M Morris, Dale W Porter, Vincent Castranova, Andrij Holian
Incomplete understanding of the contributions of dispersants and engineered nanoparticles/materials (ENM) agglomeration state to biological outcomes presents an obstacle for toxicological studies. Although reactive oxygen species (ROS) production is often regarded as the primary indicator of ENM bioactivity and toxicity, it remains unclear whether ENM produce ROS or whether ROS is an outcome of ENM-induced cell injury. Phagolysosomal disruption and cathepsin B release also promote bioactivity through inflammasome activation...
December 2016: Inhalation Toxicology
Lei Jiang, Lei Zhang, Kai Kang, Dongsheng Fei, Rui Gong, Yanhui Cao, Shangha Pan, Mingran Zhao, Mingyan Zhao
NLRP3 inflammasome plays a pivotal role in the development of acute lung injury (ALI), accelerating IL-1β and IL-18 release and inducing lung inflammation. Resveratrol, a natural phytoalexin, has anti-inflammatory properties via inhibition of oxidation, leukocyte priming, and production of inflammatory mediators. In this study, we aimed to investigate the effect of resveratrol on NLRP3 inflammasome in lipopolysaccharide-induced ALI. Mice were intratracheally instilled with 3mg/kg lipopolysaccharide (LPS) to induce ALI...
December 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Lei Jiang, Dongsheng Fei, Rui Gong, Wei Yang, Wei Yu, Shangha Pan, Mingran Zhao, Mingyan Zhao
OBJECTIVE: Accumulated studies suggest that exogenously administered carbon monoxide is beneficial for the resolution of acute lung inflammation. The present study aimed to examine the effects and the underlying mechanisms of CORM-2 on thioredoxin-interacting protein (TXNIP)/NLRP3 inflammasome pathway in lipopolysaccharide (LPS)-induced acute lung injury (ALI). METHODS: ALI was intratracheally induced by LPS in C57BL6 mice. CORM-2 or iCORM-2 (30mg/kg i.p.) was administered immediately before LPS instillation...
November 2016: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
Yuefei Jin, Weidong Wu, Weiguo Zhang, Yang Zhao, Yongjun Wu, Guoyin Ge, Yue Ba, Qiang Guo, Tianyu Gao, Xuejing Chi, Huiyun Hao, Jing Wang, Feifei Feng
Epidemiological studies have shown that exposure to ambient fine particulate matter (PM2.5 ) is associated with respiratory diseases. Lung inflammation is a central feature of many pulmonary diseases, which can be induced by PM2.5 exposure. However, the mechanisms underlying PM2.5 -induced lung inflammation remain unclear. To characterize the role of epidermal growth factor receptor (EGFR) and inflammasome in PM2.5 -induced lung inflammation in mice, 30 BALB/c mice were intrabroncheally instilled with saline and PM2...
April 2017: Environmental Toxicology
Ning Yin, Zhendan Peng, Bin Li, Jiangyan Xia, Zhen Wang, Jing Yuan, Lei Fang, Xinjiang Lu
Nucleotide-binding domains and leucine-rich repeat (NLR) pyrin domains containing 3 (NLRP3) inflammasome are highly involved in the pathogenesis of acute lung injury (ALI) wherein alveolar macrophages (AMs) play a crucial role. Isoflurane (ISO) has been shown to attenuate ALI. However, the inhibitory effects of ISO on NLRP3 activation in lipopolysaccharide (LPS)-induced ALI remain unknown. Here, we showed that 1.4% ISO post-treatment reduced LPS-induced body weight loss, pulmonary histopathological injury, edema, and vascular permeability in rats...
2016: American Journal of Translational Research
Cheng Song, Lujuan He, Jin Zhang, Hong Ma, Xiangning Yuan, Gaoyun Hu, Lijian Tao, Jian Zhang, Jie Meng
Interleukin (IL)-1β plays an important role in the pathogenesis of idiopathic pulmonary fibrosis. The production of IL-1β is dependent upon caspase-1-containing multiprotein complexes called inflammasomes and IL-1R1/MyD88/NF-κB pathway. In this study, we explored whether a potential anti-fibrotic agent fluorofenidone (FD) exerts its anti-inflammatory and anti-fibrotic effects through suppressing activation of NACHT, LRR and PYD domains-containing protein 3 (NALP3) inflammasome and the IL-1β/IL-1R1/MyD88/NF-κB pathway in vivo and in vitro...
November 2016: Journal of Cellular and Molecular Medicine
Luanqing Che, Yan Jin, Chao Zhang, Tianwen Lai, Hongbin Zhou, Lixia Xia, Baoping Tian, Yun Zhao, Juan Liu, Yinfang Wu, Yanping Wu, Jie Du, Wen Li, Songmin Ying, Zhihua Chen, Huahao Shen
Ozone is a common environmental air pollutant leading to respiratory illness. The mechanisms regulating ozone-induced airway inflammation remain poorly understood. We hypothesize that ozone-triggered inflammasome activation and interleukin (IL)-1 production regulate neutrophilic airway inflammation through IL-17A. Pulmonary neutrophilic inflammation was induced by extended (72 h) low-dose (0.7 ppm) exposure to ozone. IL-1 receptor 1 (Il1r1)(-/-), Il17a(-/-) mice and the caspase-1 inhibitor acetyl-YVAD-chloromethylketone (Ac-YVAD-cmk) were used for in vivo studies...
January 7, 2016: Scientific Reports
Shui-Xing Yu, Chong-Tao Du, Wei Chen, Qian-Qian Lei, Ning Li, Shuai Qi, Xiao-Jing Zhang, Gui-Qiu Hu, Xu-Ming Deng, Wen-Yu Han, Yong-Jun Yang
Inflammasomes are cytoplasmic, multiprotein complexes that trigger caspase-1 activation and IL-1β maturation in response to diverse stimuli. Although inflammasomes play important roles in host defense against microbial infection, overactive inflammasomes are deleterious and lead to various autoinflammatory diseases. In the current study, we demonstrated that genipin inhibits the induction of IL-1β production and caspase-1 activation by NLRP3 and NLRC4 inflammasomes. Furthermore, genipin specifically prevented NLRP3-mediated, but not NLRC4-mediated, ASC oligomerization...
December 11, 2015: Scientific Reports
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