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https://www.readbyqxmd.com/read/28683296/inflammasomes-on-the-crossroads-of-innate-immune-recognition-and-metabolic-control
#1
REVIEW
Tomasz Próchnicki, Eicke Latz
Inflammasomes are protein complexes formed upon encounter of microbial or damage-associated stimuli. The main output of inflammasome assembly is activation of caspase-1, a protease involved in both pro-inflammatory and host-protective responses. Defined bacterial or viral ligands have been identified for the inflammasome-forming receptors AIM2, NLRP1, and NLRC4. The signals activating other inflammasomes, NLRP3, NLRP6, and pyrin, are less well understood. Recent studies implicated several low-molecular-weight compounds traditionally linked to metabolism, not immunity, in modulation of inflammasome signaling...
July 5, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28663562/expression-analysis-of-inflammasome-sensors-and-implication-of-nlrp12-inflammasome-in-prostate-cancer
#2
Dev Karan, Ossama Tawfik, Seema Dubey
Inflammasomes are multi-proteins complex regulating inflammation-associated signaling. While inflammation plays a critical role in cancer cell growth, studies remain uncharacterized on the role of inflammasomes in prostate cancer. Using Gene Expression Omnibus (GEO) public datasets, we screened the expression profiles of inflammasome sensors NLRP3, NLRC4, NLRP6, NRLP12, and AIM2 in prostate tumor tissues, and verified their mRNA level in a panel of prostate cancer cell lines. The selected expression of NLRP3 and NLRP12 inflammasomes was validated, and the clinical association was evaluated in human prostate archival tumor tissues...
June 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28591587/nlrp6-protects-il10-mice-from-colitis-by-limiting-colonization-of-akkermansia-muciniphila
#3
Sergey S Seregin, Natasha Golovchenko, Bryan Schaf, Jiachen Chen, Nicholas A Pudlo, Jonathan Mitchell, Nielson T Baxter, Lili Zhao, Patrick D Schloss, Eric C Martens, Kathryn A Eaton, Grace Y Chen
No abstract text is available yet for this article.
June 6, 2017: Cell Reports
https://www.readbyqxmd.com/read/28479336/desiccating-stress-worsens-alkali-burn-injury-by-magnifying-caspase-8-induced-imbalance-of-nlrp3-and-nlrp6
#4
Xia Hua, Xiaoyong Yuan, Yonghao Li, Hui Chen, Jin Yuan, Silvia Tanumiharjo, Fang Bian, Lishi Su, Yanhua Hong, Yizhi Liu, Wei Chi
No abstract text is available yet for this article.
May 4, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28468094/-effects-of-allogeneic-hematopoietic-stem-cell-transplantation-in-combination-with-infusion-of-endothelial-progenitor-cells-on-bone-marrow-inflammatory-injury
#5
W Li, M F Li, P P Zhao, J L Qiao, K L Xu, L Y Zeng
Objective: To explore effects of allogeneic hematopoietic stem cell transplantation (HSCT) in combination with infusion of endothelial progenitor cells (EPC) on bone marrow inflammatory injury. Methods: 6-8 weeks BALB/c (H-2K(d)) mice after lethal dose of irradiation (TBI) were subjected to allogeneic bone marrow transplantation (BMT group) or co-transplantation of EPC (EPC group) . Samples of bone marrow cells of mice in each group on days 7,14,21,28 after transplantation were obtained to detect EPC cultural and cell chimeric rates by flow cytometer...
April 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/28445725/nlrp6-protects-il10-mice-from-colitis-by-limiting-colonization-of-akkermansia-muciniphila
#6
Sergey S Seregin, Natasha Golovchenko, Bryan Schaf, Jiachen Chen, Nicholas A Pudlo, Jonathan Mitchell, Nielson T Baxter, Lili Zhao, Patrick D Schloss, Eric C Martens, Kathryn A Eaton, Grace Y Chen
Dysfunction in host immune responses and pathologic alterations in the gut microbiota, referred to as dysbiosis, can both contribute to the development of inflammatory bowel disease (IBD). However, it remains unclear how specific changes in host immunity or the microbiota cause disease. We previously demonstrated that the loss of the innate immune receptor NLRP6 in mice resulted in impaired production of interleukin-18 (IL-18) and increased susceptibility to epithelial-induced injury. Here, we show that NLRP6 is important for suppressing the development of spontaneous colitis in the Il10(-/-) mice model of IBD and that NLRP6 deficiency results in the enrichment of Akkermansia muciniphila...
April 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28238526/mitochondrial-dna-oxidation-induces-imbalanced-activity-of-nlrp3-nlrp6-inflammasomes-by-activation-of-caspase-8-and-brcc36-in-dry-eye
#7
Wei Chi, Xia Hua, Xin Chen, Fang Bian, Xiaoyong Yuan, Lili Zhang, Xiaoran Wang, Ding Chen, Ruzhi Deng, Zhijie Li, Yizhi Liu, Cintia S de Paiva, Stephen C Pflugfelder, De-Quan Li
The concept of innate immunity has been expanded to recognize environmental pathogens other than microbial components. However, whether and how the innate immunity is initiated by epithelium in response to environmental physical challenges such as low humidity and high osmolarity in an autoimmune disease, dry eye, is still largely unknown. Using two experimental dry eye models, primary human corneal epithelial cultures exposed to hyperosmolarity and mouse ocular surface facing desiccating stress, we uncovered novel innate immunity pathway by ocular surface epithelium, where oxidized mitochondrial DNA induces imbalanced activation of NLRP3/NLRP6 inflammasomes via stimulation of caspase-8 and BRCC36 in response to environmental stress...
June 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28214100/nlrp6-a-multifaceted-innate-immune-sensor
#8
REVIEW
Maayan Levy, Hagit Shapiro, Christoph A Thaiss, Eran Elinav
NLRP6, a member of the nucleotide-binding domain, leucine-rich repeat-containing (NLR) innate immune receptor family, regulates inflammation and host defense against microorganisms. Similar to other NLRs, NLRP6 not only participates in inflammasome formation, but is also involved in nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling regulation and facilitation of gastrointestinal antiviral effector functions. Additionally, NLRP6 contributes to the regulation of mucus secretion and antimicrobial peptide production, thereby impacting intestinal microbial colonization and associated microbiome-related infectious, autoinflammatory, metabolic, and neoplastic diseases...
April 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28175270/p776-dysbiosis-in-nlrp6-asc-deficient-mice-does-not-result-from-inflammasome-deficiency
#9
M Mamantopoulos, F Ronchi, F Van Hauwermeiren, S Vieira-Silva, B Yilmaz, L Martens, Y Saeys, S Drexler, A Yazdi, J Raes, M Lamkanfi, K McCoy, A Wullaert
No abstract text is available yet for this article.
February 1, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/28095655/production-of-il-1%C3%AE-and-inflammasome-with-up-regulated-expressions-of-nod-like-receptor-related-genes-in-toxoplasma-gondii-infected-thp-1-macrophages
#10
Jia-Qi Chu, Ge Shi, Yi-Ming Fan, In-Wook Choi, Guang-Ho Cha, Yu Zhou, Young-Ha Lee, Juan-Hua Quan
Toxoplasma gondii is an obligate intracellular parasite that stimulates production of high levels of proinflammatory cytokines, which are important for innate immunity. NLRs, i.e., nucleotide-binding oligomerization domain (NOD)-like receptors, play a crucial role as innate immune sensors and form multiprotein complexes called inflammasomes, which mediate caspase-1-dependent processing of pro-IL-1β. To elucidate the role of inflammasome components in T. gondii-infected THP-1 macrophages, we examined inflammasome-related gene expression and mechanisms of inflammasome-regulated cytokine IL-1β secretion...
December 2016: Korean Journal of Parasitology
https://www.readbyqxmd.com/read/28093447/inflammasomes-and-cancer
#11
Rajendra Karki, Si Ming Man, Thirumala-Devi Kanneganti
Inflammation affects all stages of tumorigenesis. A key signaling pathway leading to acute and chronic inflammation is through activation of the caspase-1 inflammasome. Inflammasome complexes are assembled on activation of certain nucleotide-binding domain, leucine-rich repeat-containing proteins (NLR), AIM2-like receptors, or pyrin. Of these, NLRP1, NLRP3, NLRC4, NLRP6, and AIM2 influence the pathogenesis of cancer by modulating innate and adaptive immune responses, cell death, proliferation, and/or the gut microbiota...
February 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/27788256/p2y1-receptor-signaling-contributes-to-high-salt-induced-priming-of-the-nlrp3-inflammasome-in-retinal-pigment-epithelial-cells
#12
Philipp Prager, Margrit Hollborn, Anja Steffen, Peter Wiedemann, Leon Kohen, Andreas Bringmann
BACKGROUND: Systemic hypertension is a risk factor of age-related macular degeneration (AMD), a chronic inflammatory disease. Acute hypertension is caused by increased extracellular osmolarity after intake of dietary salt (NaCl). We determined in cultured human retinal pigment epithelial (RPE) cells whether high extracellular NaCl alters the gene expression of inflammasome-associated proteins, and whether autocrine/paracrine purinergic (P2) receptor signaling contributes to the NaCl-induced NLRP3 gene expression...
2016: PloS One
https://www.readbyqxmd.com/read/27397068/inflammasome-as-a-key-pathogenic-mechanism-in-endometriosis
#13
Pedro Bullon, Jose Manuel Navarro
BACKGROUND: Endometriosis remains a challenging condition for clinicians to treat. To improve our results, we have to develop new treatment strategies based on pathophysiological mechanisms targeting the etiologic and pathogenic processes involved. OBJECTIVES: Revise new inflammatory pathogenic mechanisms involved in endometriosis, namely inflammasome. METHOD: Literature review for the updating of data to give new clues for different options of treatments...
2017: Current Drug Targets
https://www.readbyqxmd.com/read/27353251/nlrp6-function-in-inflammatory-monocytes-reduces-susceptibility-to-chemically-induced-intestinal-injury
#14
S S Seregin, N Golovchenko, B Schaf, J Chen, K A Eaton, G Y Chen
NLRP6 is a member of the Nod-like receptor family, whose members are involved in the recognition of microbes and/or tissue injury. NLRP6 was previously demonstrated to regulate the production of interleukin (IL)-18 and is important for protecting mice against chemically induced intestinal injury and colitis-associated colon cancer. However, the cellular mechanisms by which NLRP6 reduces susceptibility to colonic inflammation remain unclear. Here, we determined that NLRP6 expression is specifically upregulated in Ly6C(hi) inflammatory monocytes that infiltrate into the colon during dextran sulfate sodium (DSS)-induced inflammation...
March 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/27339979/a-sentinel-goblet-cell-guards-the-colonic-crypt-by-triggering-nlrp6-dependent-muc2-secretion
#15
George M H Birchenough, Elisabeth E L Nyström, Malin E V Johansson, Gunnar C Hansson
Innate immune signaling pathways contribute to the protection of host tissue when bacterially challenged. Colonic goblet cells are responsible for generating the two mucus layers that physically separate the luminal microbiota from the host epithelium. Analysis of colonic tissues from multiple mouse strains allowed us to identify a "sentinel" goblet cell (senGC) localized to the colonic crypt entrance. This cell nonspecifically endocytoses and reacts to the TLR2/1, TLR4, and TLR5 ligands by activating the Nlrp6 inflammasome downstream of TLR- and MyD88-dependent Nox/Duox reactive oxygen species synthesis...
June 24, 2016: Science
https://www.readbyqxmd.com/read/27221480/atypical-inflammasomes
#16
Ann M Janowski, Fayyaz S Sutterwala
Pattern recognition receptors, including members of the NLR and PYHIN families, are essential for recognition of both pathogen- and host-derived danger signals. A number of molecules in these families are capable of forming multiprotein complexes termed inflammasomes that result in the activation of caspase-1. In addition to NLRP1, NLRP3, NLRC4, and AIM2, which form well-described inflammasome complexes, IFI16, NLRP6, NLRP7, NLRP12, and NLRC5 have also been proposed to form inflammasomes under specific conditions...
2016: Methods in Molecular Biology
https://www.readbyqxmd.com/read/26945813/role-of-inflammasome-genetics-in-susceptibility-to-hpv-infection-and-cervical-cancer-development
#17
A Pontillo, P Bricher, V N C Leal, S Lima, P R E Souza, S Crovella
PROBLEM: Only a small proportion of HPV+ women develop virus-associated lesions and cervical cancer, suggesting that other factors are involved in HPV+ keratinocyte transformation. Immune response plays an important role in clearing HPV infection, and host genetic variants resulting in defective immune response have been associated with virus persistence and/or cervical cancer. Considering that genetic variations in inflammasome genes were previously associated with viral infection and cancer development, the present study investigates selected single nucleotide polymorphisms (SNPs) in inflammasome genes as a possible risk factor for HPV infection susceptibility and/or for progression to cervical cancer...
September 2016: Journal of Medical Virology
https://www.readbyqxmd.com/read/26869766/amelioration-of-concanavalin-a-induced-autoimmune-hepatitis-by-magnesium-isoglycyrrhizinate-through-inhibition-of-cd4-cd25-cd69-subset-proliferation
#18
Qi Yang, Jianwei Wang, Ran Liu, Zhiqiang Wang, Yufeng Li, Yifan Zhang, Xiaohua Hao, Yubo Huang, Wen Xie, Hongshan Wei
Magnesium isoglycyrrhizinate (MGL) is a new stereoisomer of glycyrrhizic acid, which is clinically used as a hepatoprotective medicine with more potent effects and less side effects than glycyrrhizic acid. This study was designed to evaluate the protective effects and possible mechanism of MGL against concanavalin A (Con A)-induced autoimmune hepatitis. Hepatitis was induced by Con A in C57/6J mice with or without MGL administration; injury score and serum ALT were evaluated. The CD4(+) T-cells were isolated from splenocytes and challenged with Con A after coculturing with MGL...
2016: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/26711333/nuclear-retention-of-mrna-in-mammalian-tissues
#19
Keren Bahar Halpern, Inbal Caspi, Doron Lemze, Maayan Levy, Shanie Landen, Eran Elinav, Igor Ulitsky, Shalev Itzkovitz
mRNA is thought to predominantly reside in the cytoplasm, where it is translated and eventually degraded. Although nuclear retention of mRNA has a regulatory potential, it is considered extremely rare in mammals. Here, to explore the extent of mRNA retention in metabolic tissues, we combine deep sequencing of nuclear and cytoplasmic RNA fractions with single-molecule transcript imaging in mouse beta cells, liver, and gut. We identify a wide range of protein-coding genes for which the levels of spliced polyadenylated mRNA are higher in the nucleus than in the cytoplasm...
December 29, 2015: Cell Reports
https://www.readbyqxmd.com/read/26660940/mucosal-barrier-depletion-and-loss-of-bacterial-diversity-are-primary-abnormalities-in-paediatric-ulcerative-colitis
#20
Misagh Alipour, Deenaz Zaidi, Rosica Valcheva, Juan Jovel, Inés Martínez, Consolato Sergi, Jens Walter, Andrew L Mason, Gane Ka-Shu Wong, Levinus A Dieleman, Matthew W Carroll, Hien Q Huynh, Eytan Wine
BACKGROUND AND AIMS: Ulcerative colitis [UC] is associated with colonic mucosa barrier defects and bacterial dysbiosis, but these features may simply be the result of inflammation. Therefore, we sought to assess whether these features are inherently abrogated in the terminal ileum [TI] of UC patients, where inflammation is absent. METHODS: TI biopsies from paediatric inflammatory bowel disease [IBD] subsets [Crohn's disease [CD; n = 13] and UC [n = 10]], and non-IBD disease controls [n = 12] were histologically graded, and alcian blue/periodic acid-Schiff stained biopsies were quantified...
April 2016: Journal of Crohn's & Colitis
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