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https://www.readbyqxmd.com/read/27909054/identification-of-a-substrate-selective-exosite-within-the-metalloproteinase-anthrax-lethal-factor
#1
Allison B Goldberg, Eunice Cho, Chad J Miller, Hua Jane Lou, Benjamin E Turk
The metalloproteinase anthrax lethal factor (LF) is secreted by Bacillus anthracis to promote disease virulence through disruption of host signaling pathways. LF is a highly specific protease, exclusively cleaving mitogen-activated protein kinase kinases (MKKs) and rodent NACHT leucine-rich repeat and pyrin domain containing protein 1B (NLRP1B). How LF achieves such restricted substrate specificity is not understood. Previous studies have suggested the existence of an exosite interaction between LF and MKKs that promotes cleavage efficiency and specificity...
December 1, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27906774/lessons-from-characterization-and-treatment-of-the-autoinflammatory-syndromes
#2
Ivona Aksentijevich, Michael F McDermott
PURPOSE OF REVIEW: The list of genes associated with systemic inflammatory diseases has been steadily growing because of the explosion of new genomic technologies. Significant advances in the past year have deepened our understanding of the molecular mechanisms linked to inflammation and elucidated insights on the efficacy of specific therapies for these and related conditions. We review the molecular pathogenesis of four recently characterized monogenic autoinflammatory diseases: haploinsufficiency of A20, otulipenia, a severe form of pyrin-associated disease, and a monogenic form of systemic juvenile idiopathic arthritis...
November 30, 2016: Current Opinion in Rheumatology
https://www.readbyqxmd.com/read/27904671/melatonin-promotes-diabetic-wound-healing-in-vitro-by-regulating-keratinocyte-activity
#3
Ruipeng Song, Lijun Ren, Haoli Ma, Ruijing Hu, Honghong Gao, Li Wang, Xuehui Chen, Zhigang Zhao, Jialin Liu
Diabetic patients are at high risk of developing delayed cutaneous wound healing. Proper keratinocyte proliferation and migration are crucial steps during re-epithelialization. Melatonin (Mel) accelerates wound repair in full-thickness incisional wounds; however, its role in diabetic wound healing is unknown. This study explored the role of Mel in diabetic wound healing in vitro by using high glucose (HG)-cultured keratinocytes. Mel reduced the HG-induced mRNA expression and release of pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin (IL)-1β, IL-6, and IL-8, in keratinocytes...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27875342/the-multifaceted-roles-of-inflammasome-proteins-in-cancer
#4
Virginie Petrilli
PURPOSE OF REVIEW: Inflammasomes are major actors of the innate immune system, through their regulation of inflammatory caspases and maturation of IL-1β and IL-18. These multiprotein complexes have been shown to play major roles in inflammatory and metabolic diseases and have more recently been implicated in tumor development and dissemination. In this review, we address these recent findings, focusing particularly on colorectal cancer (CRC) initiation and tumor dissemination. RECENT FINDINGS: Based mostly on loss-of-function experiments in mouse models, paradoxical results were obtained as both protumoral and antitumoral activities were reported...
January 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/27872860/danggui-buxue-tang-attenuates-tubulointerstitial-fibrosis-via-suppressing-nlrp3-inflammasome-in-a-rat-model-of-unilateral-ureteral-obstruction
#5
Linna Wang, Jiwei Ma, Cunxia Guo, Changyong Chen, Zhong Yin, Xueguang Zhang, Xiangmei Chen
Inflammation significantly contributes to the progression of chronic kidney disease (CKD). This study aimed to characterize Danggui Buxue Tang (DBT) renoprotection and relationship with NOD-like receptors family pyrin domain-containing 3 (NLRP3) inflammasome expression in rats with unilateral ureteral obstruction (UUO). Sprague-Dawley rats were subjected to UUO and randomly assigned to untreated UUO, enalapril-treated (10 mg/kg/day), and DBT-treated (9 g/kg/day) groups. Sham-operated rats served as controls, with 8 rats in each group...
2016: BioMed Research International
https://www.readbyqxmd.com/read/27864974/nlrp3-inflammasome-may-regulate-inflammatory-response-of-human-periodontal-ligament-fibroblasts-in-an-apoptosis-associated-speck-like-protein-containing-a-card-asc-dependent-manner
#6
W L Lu, D Z Song, J L Yue, T T Wang, X D Zhou, P Zhang, L Zhang, D M Huang
AIM: To explore the role of NLRP3 (NACHT [nucleotide-binding oligomerization], LRR [leucine-rich repeat] and PYD [pyrin domain] domains-containing protein 3) inflammasome in the inflammatory response of human periodontal ligament fibroblasts (HPDLFs). METHODOLOGY: The expression of NLRP3 and apoptosis-associated speck-like protein containing a CARD (ASC) in inflammatory periapical tissues and HPDLFs was examined by immunohistochemical and immunofluorescent staining...
November 19, 2016: International Endodontic Journal
https://www.readbyqxmd.com/read/27864235/l5-ldl-from-st-elevation-myocardial-infarction-patients-induces-il-1%C3%AE-production-via-lox-1-and-nlrp3-inflammasome-activation-in-macrophages
#7
Tzu-Ching Yang, Po-Yuan Chang, Shao-Chun Lu
L5-LDL, the most electronegative LDL associated with major cardiovascular risks, significantly rises in patients with ST-segment elevation myocardial infarction (STEMI). The inflammatory nature of atherosclerotic vascular diseases has prompted us to investigate whether L5-LDL induces the production of inflammatory cytokines, especially vascular ischemia-related interleukin (IL)-1β in the pathogenesis of STEMI. Clinical data showed that plasma levels of L5-LDL and IL-1β were higher in the STEMI patients than in the controls (p < 0...
November 18, 2016: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/27862176/inflammasomes-hormesis-and-antioxidants-in-neuroinflammation-role-of-nrlp3-in-alzheimer-disease
#8
REVIEW
Manuela Pennisi, Rosalia Crupi, Rosanna Di Paola, Maria Laura Ontario, Rita Bella, Edward J Calabrese, Roberto Crea, Salvatore Cuzzocrea, Vittorio Calabrese
Alzheimer disease (AD) is a progressive neurodegenerative disorder leading to cognitive decline, neuropsychiatric symptoms, disability, caregiver burden, and premature death. It represents the most prevalent cause of dementia, and its incidence rates exponentially increase with increasing age. The number of Americans living with AD is rapidly increasing. An estimated 5.4 million Americans of all ages have AD in 2016. One in nine people aged 65 and older has AD, and by midcentury, someone in the United States will develop the disease every 33 sec...
November 8, 2016: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/27852921/a-role-for-the-inflammasome-in-spontaneous-labor-at-term-with-acute-histologic-chorioamnionitis
#9
Nardhy Gomez-Lopez, Roberto Romero, Yi Xu, Olesya Plazyo, Ronald Unkel, Nandor Gabor Than, Piya Chaemsaithong, Tinnakorn Chaiworapongsa, Zhong Dong, Adi L Tarca, Vikki M Abrahams, Lami Yeo, Sonia S Hassan
Inflammasomes are cytosolic signaling platforms that regulate the activation of caspase (CASP)-1, which induces the maturation of interleukin (IL)-1β and IL-18. Herein, we determined whether the chorioamniotic membranes from women in spontaneous labor at term with acute histologic chorioamnionitis express major inflammasome components and whether these changes are associated with the activation of CASP-1 and CASP-4 and the release of mature IL-1β and IL-18. When comparing the chorioamniotic membranes from women in spontaneous labor at term with acute histologic chorioamnionitis to those without this placental lesion, we found that (1) the messenger RNA (mRNA) abundance of NLR family pyrin domain containing 3 (NLRP3), NLR family CARD domain containing 4 (NLRC4), absent in melanoma 2 (AIM2), and nucleotide binding oligomerization domain 2 (NOD2) was higher; (2) the NLRP3 and NLRC4 protein quantities were increased; (3) the mRNA and protein expressions of CASP-1 and its active forms were greater; (4) CASP-4 was increased at the mRNA level only; (5) the mRNA and protein expressions of IL-1β and its mature form were higher; and (6) a modest increase in the total protein concentration and abundance of the mature form of IL-18 was observed...
November 16, 2016: Reproductive Sciences
https://www.readbyqxmd.com/read/27847555/sulforaphane-protects-pancreatic-acinar-cell-injury-by-modulating-nrf2-mediated-oxidative-stress-and-nlrp3-inflammatory-pathway
#10
Zhaojun Dong, Haixiao Shang, Yong Q Chen, Li-Long Pan, Madhav Bhatia, Jia Sun
Acute pancreatitis (AP) is characterized by early activation of intra-acinar proteases followed by acinar cell death and inflammation. Cellular oxidative stress is a key mechanism underlying these pathological events. Sulforaphane (SFN) is a natural organosulfur antioxidant with undescribed effects on AP. Here we investigated modulatory effects of SFN on cellular oxidation and inflammation in AP. AP was induced by cerulean hyperstimulation in BALB/c mice. Treatment group received a single dose of 5 mg/kg SFN for 3 consecutive days before AP...
2016: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/27826011/roles-of-the-nlrp3-inflammasome-in-the-pathogenesis-of-diabetic-nephropathy
#11
REVIEW
Yuan-Ye Qiu, Li-Qin Tang
Diabetic nephropathy (DN) is a serious complication of diabetes mellitus, and persistent inflammation in circulatory and renal tissues is an important pathophysiological basis for DN. The essence of the microinflammatory state is the innate immune response, which is central to the occurrence and development of DN. Members of the inflammasome family, including both "receptors" and "regulators", are key to the inflammatory immune response. Nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) and other inflammasome components are able to detect endogenous danger signals, resulting in activation of caspase-1 as well as interleukin (IL)-1β, IL-18 and other cytokines; these events stimulate the inflammatory cascade reaction, which is crucial for DN...
November 5, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/27819323/donor-and-recipient-genetic-variants-in-nlrp3-associate-with-early-acute-rejection-following-kidney-transplantation
#12
Mark C Dessing, Jesper Kers, Jeffrey Damman, Gerjan J Navis, Sandrine Florquin, Jaklien C Leemans
NLRP3 (NOD-like receptor family, pyrin domain containing 3) is a member of the inflammasome family and is of special interest in renal disease. Experimental studies have shown that Nlrp3 plays a significant role in the induction of renal damage and dysfunction in acute and chronic renal injury. However, the role of NLRP3 in human renal disease is completely unknown. From a retrospective cohort study, we determined in 1271 matching donor and recipient samples if several NLRP3 single nucelotide polymorphisms (SNPs) were associated with primary non-function (PNF), delayed graft function (DGF), biopsy-proven acute rejection (BPAR) and death-censored graft and patient survival...
November 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27807222/the-emerging-role-of-thioredoxin-interacting-protein-in-myocardial-ischemia-reperfusion-injury
#13
Bing F Wang, Jun Yoshioka
Myocardial ischemia/reperfusion injury represents a major threat to human health and contributes to adverse cardiovascular outcomes worldwide. Despite the identification of numerous molecular mechanisms, understanding of the complex pathophysiology of this clinical syndrome remains incomplete. Thioredoxin-interacting protein (Txnip) has been of great interest in the past decade since it has been reported to be a critical regulator in human diseases with several important cellular functions. Thioredoxin-interacting protein binds to and inhibits thioredoxin, a redox protein that neutralizes reactive oxygen species (ROS), and through its interaction with thioredoxin, Txnip sensitizes cardiomyocytes to ROS-induced apoptosis...
November 2, 2016: Journal of Cardiovascular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/27785882/naoxintong-attenuates-ischaemia-reperfusion-injury-through-inhibiting-nlrp3-inflammasome-activation
#14
Yaqiong Wang, Xiaoxiang Yan, Shouling Mi, Zhang Li, Yuexiang Wang, Hong Zhu, Xiaolei Sun, Buchang Zhao, Chao Zhao, Yunzeng Zou, Kai Hu, Xiaoqiang Ding, Aijun Sun, Junbo Ge
Naoxintong (NXT) is a Chinese Materia Medica standardized product extracted from 16 various kinds of Chinese traditional herbal medicines including Salvia miltiorrhiza, Angelica sinensis, Astragali Radix. Naoxintong is clinically effective in treating ischaemia heart disease. Nucleotide-binding oligomerization domain-Like Receptor with a Pyrin domain 3 (NLRP3) inflammasome has been critically involved in myocardial ischaemia/reperfusion (I/R) injury. Here, we have been suggested that NXT might attenuate myocardial I/R injury via suppression of NLRP3 inflammasome activation...
October 26, 2016: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/27783111/contribution-of-redox-dependent-activation-of-endothelial-nlrp3-inflammasomes-to-hyperglycemia-induced-endothelial-dysfunction
#15
Yang Chen, Lei Wang, Ashley L Pitzer, Xiang Li, Pin-Lan Li, Yang Zhang
: Recent studies indicate that inflammasomes serve as intracellular machinery to initiate classical cytokine-mediated inflammatory responses and play a crucial role in the pathogenesis of cardiovascular diseases. However, whether or not the activation of endothelial inflammasomes directly causes cell dysfunction or tissue injury without recruitment of inflammatory cells is unknown. We explored the role of endothelial cell inflammasome activation in mediating tight junction disruption, a hallmark event of endothelial barrier dysfunction leading to endothelial hyperpermeability in diabetes...
October 25, 2016: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/27780404/autophagy-induced-by-axl-receptor-tyrosine-kinase-alleviates-acute-liver-injury-via-inhibition-of-nlrp3-inflammasome-activation-in-mice
#16
Jihye Han, Joonbeom Bae, Chang-Yong Choi, Sang-Pil Choi, Hyung-Sik Kang, Eun-Kyeong Jo, Jongsun Park, Young Sik Lee, Hyun-Seuk Moon, Chung-Gyu Park, Myung-Shik Lee, Taehoon Chun
Severe hepatic inflammation is a common cause of acute or chronic liver disease. Macrophages are one of the key mediators which regulate the progress of hepatic inflammation. Increasing evidence shows that the TAM (TYRO3, AXL and MERTK) family of RTKs (receptor tyrosine kinases), which is expressed in macrophages, alleviates inflammatory responses through a negative feedback loop. However, the functional contribution of each TAM family member to the progression of hepatic inflammation remains elusive. In this study, we explore the role of individual TAM family proteins during autophagy induction and evaluate their contribution to hepatic inflammation...
October 26, 2016: Autophagy
https://www.readbyqxmd.com/read/27777559/curcumin-represses-nlrp3-inflammasome-activation-via-tlr4-myd88-nf-%C3%AE%C2%BAb-and-p2x7r-signaling-in-pma-induced-macrophages
#17
Fanqi Kong, Bozhi Ye, Jiatian Cao, Xueli Cai, Lu Lin, Shanjun Huang, Weijian Huang, Zhouqing Huang
Aims: In the NOD-like receptor (NLR) family, the pyrin domain containing 3 (NLRP3) inflammasome is closely related to the progression of atherosclerosis. This study aimed to assess the effects of curcumin on NLRP3 inflammasome in phorbol 12-myristate 13-acetate (PMA)-induced macrophages and explore its underlying mechanism. Methods: Human monocytic THP-1 cells were pretreated with curcumin for 1 h and subsequently induced with PMA for 48 h. Total protein was collected for Western blot analysis. Cytokine interleukin (IL)-1β release and nuclear factor kappa B (NF-κB) p65 translocation were detected by ELISA assay and cellular NF-κB translocation kit, respectively...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27774934/-c1q-tumor-necrosis-factor-related-protein-6-ctrp6-is-involved-in-gentamicin-induced-acute-kidney-injury-in-rats
#18
Rong Li, Xiaoxia Yang, Yan Yu, Meilan Zhou, Xiujuan Tian, Shidong Feng, Hanmin Wang
Objective To explore the role of the anti-inflammatory cytokine C1q/tumor necrosis factor related protein 6 (CTRP6) in gentamicin-induced acute kidney injury in rats. Methods SD rats were divided into 5 groups including control group, model group and the other 3 experimental groups. The rats in model group and experimental groups were subcutaneously injected with gentamicin at the dose of 400 mg/(kg.d) for consecutive 2 days to induce acute renal injury. Two days before gentamicin injection, the rats in the 3 experimental groups were given pAd-CTRP6 at the doses of 0...
November 2016: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/27769021/the-neuroprotection-of-sinomenine-against-ischemic-stroke-in-mice-by-suppressing-nlrp3-inflammasome-via-ampk-signaling
#19
Jing Qiu, Min Wang, Jun Zhang, Qing Cai, Dan Lu, Yansong Li, Yushu Dong, Tianzhi Zhao, Huisheng Chen
Neuroinflammation remains the primary cause of morbidity and mortality in stroke-induced secondary brain injury. The NOD-like receptor pyrin 3 (NLRP3) inflammasome is involved in diverse inflammatory diseases, including cerebral ischemia, and is thus considered an effective therapeutic target. In the present study, we investigated the neuroprotection of Sinomenine (SINO), a potent natural anti-apoptotic and anti-inflammatory molecule, against cerebral ischemia in a mouse model of middle cerebral artery occlusion (MCAO) in vivo and in an oxygen glucose deprivation (OGD)-treated astrocytes/microglia model in vitro...
November 2016: International Immunopharmacology
https://www.readbyqxmd.com/read/27749344/protective-effect-of-inflammasome-activation-by-hydrogen-peroxide-in-a-mouse-model-of-septic-shock
#20
Olivier Huet, Raelene J Pickering, Chris Tikellis, Celine Latouche, Fenella Long, Bronwyn Kingwell, Bryan Dickinson, Chris J Chang, Seth Masters, Fabienne Mackay, Mark E Cooper, Judy B de Haan
OBJECTIVES: To study the effect of a lack of antioxidant defenses during lethal pneumonia induced by Klebsiella pneumonia, compared to wild-type mice. SETTING: Laboratory experiments. SUBJECTS: C57Bl6 and glutathione peroxidase 1 knockout mice. INTERVENTION: Murine acute pneumonia model induced by Klebsiella pneumonia. MEASUREMENTS AND MAIN RESULTS: We show here that despite a lack of one of the major antioxidant defense enzymes, glutathione peroxidase 1 knockout mice are protected during lethal pneumonia induced by Klebsiella pneumonia, compared to wild-type mice...
October 3, 2016: Critical Care Medicine
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