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inflammasome, inflammation, ROS, lung

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...
April 6, 2017: 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
Shichao Han, Weixia Cai, Xuekang Yang, Yanhui Jia, Zhao Zheng, Hongtao Wang, Jun Li, Yan Li, Jianxin Gao, Lei Fan, Dahai Hu
The NLRP3 inflammasome is necessary for initiating acute sterile inflammation. However, its role in the pathogenesis of burn-induced acute lung injury (ALI) is unknown. This study aimed to determine the role of the NLRP3 inflammasome and the signaling pathways involved in burn-induced ALI. We observed that the rat lungs exhibited enhanced inflammasome activity after burn, as evidenced by increased levels of NLRP3 expression and Caspase-1 activity and augmented inflammatory cytokines. Inhibition of NLRP3 inflammasome by BAY11-7082 attenuated burn-induced ALI, as demonstrated by the concomitant remission of histopathologic changes and the reduction of myeloperoxidase (MPO) activity, inflammatory cytokines in rat lung tissue, and protein concentrations in the bronchoalveolar lavage fluid (BALF)...
2015: Mediators of Inflammation
Venugopal Rajanbabu, Lakshmi Galam, Jutaro Fukumoto, Juan Enciso, Pratima Tadikonda, Troy N Lane, Sayantani Bandyopadhyay, Prasanna Tamarapu Parthasarathy, Young Cho, Seong Ho Cho, Yong Chul Lee, Richard F Lockey, Narasaiah Kolliputi
Incomplete clearance of apoptotic cells and reactive oxygen species (ROS) release are known to trigger inflammasome activation causing severe inflammation in acute lung injury and various metabolic and autoimmune diseases. Moreover, it has been reported that apoptotic cell clearance and ROS-mediated apoptosis critically depend on mitochondrial uncoupling protein-2 (UCP2). However, the relationship between UCP2 and inflammasome activation has not been studied. This report investigates the role of UCP2 in the expression and activation of NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome in human macrophages...
September 2015: Cellular Immunology
Elizabeth A Thompson, Brian C Sayers, Ellen E Glista-Baker, Kelly A Shipkowski, Alexia J Taylor, James C Bonner
The nanotechnology revolution offers enormous societal and economic benefits for innovation in the fields of engineering, electronics, and medicine. Nevertheless, evidence from rodent studies show that biopersistent engineered nanomaterials (ENMs) stimulate immune, inflammatory, and fibroproliferative responses in the lung, suggesting possible risks for lung diseases or systemic immune disorders as a consequence of occupational, environmental, or consumer exposure. Due to their nanoscale dimensions and increased surface area per unit mass, ENMs have a much greater potential to reach the distal regions of the lung and generate ROS...
July 2014: Journal of Environmental Immunology and Toxicology
Kuo-Feng Hua, Ju-Ching Chou, Yulin Lam, Yu-Ling Tasi, Ann Chen, Shuk-Man Ka, Zhanxiong Fang, May-Lan Liu, Feng-Ling Yang, Yu-Liang Yang, Yi-Chich Chiu, Shih-Hsiung Wu
Two polyenylpyrroles from a soil ascomycete Gymnoascus reessii were previously identified as hit compounds in screening for cytotoxicity against lung cancer cells. These compounds and various analogs, which have been previously synthesized and tested for anti-lung cancer cell activity, were tested for anti-inflammatory activity. After preliminary screening for cytotoxicity for RAW 264.7 murine macrophage cells, the non-toxic compounds were tested for anti-inflammatory activity using lipopolysaccharide (LPS)-activated RAW 264...
2013: PloS One
Jutaro Fukumoto, Itsuko Fukumoto, Prasanna Tamarapu Parthasarathy, Ruan Cox, Bao Huynh, Gurukumar Kollongod Ramanathan, Rajan Babu Venugopal, Diane S Allen-Gipson, Richard F Lockey, Narasaiah Kolliputi
Inspiration of a high concentration of oxygen, a therapy for acute lung injury (ALI), could unexpectedly lead to reactive oxygen species (ROS) production and hyperoxia-induced acute lung injury (HALI). Nucleotide-binding domain and leucine-rich repeat PYD-containing protein 3 (NLRP3) senses the ROS, triggering inflammasome activation and interleukin-1β (IL-1β) production and secretion. However, the role of NLRP3 inflammasome in HALI is unclear. The main aim of this study is to determine the effect of NLRP3 gene deletion on inflammatory response and lung epithelial cell death...
July 15, 2013: American Journal of Physiology. Cell Physiology
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