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IL 17 receptor B

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https://www.readbyqxmd.com/read/28546429/structural-studies-unravel-the-active-conformation-of-apo-ror%C3%AE-t-nuclear-receptor-and-a-common-inverse-agonism-of-two-diverse-classes-of-ror%C3%AE-t-inhibitors
#1
Xiang Li, Marie Anderson, Delphine Collin, Ingo Muegge, John Wan, Debra Brennan, Stanley Kugler, Donna Terenzio, Charles Kennedy, Siqi Lin, Mark E Labadia, Brian Cook, Robert Hughes, Neil A Farrow
The nuclear receptor retinoid acid-related orphan receptor γt (RORγt) is a master regulator of the Th17/IL-17 pathway that plays crucial roles in the pathogenesis of autoimmunity. RORγt has recently emerged as a highly promising target for treatment of a number of autoimmune diseases. Through high-throughput screening we previously identified several classes of inverse agonists for RORγt. Here, we report the crystal structures for the ligand binding domain of RORγt in both apo and ligand-bound states. We show that apo RORγt adopts an active conformation capable of recruiting coactivator peptides and present a detailed analysis of the structural determinants that stabilize helix 12 (H12) of RORγt in the active state in the absence of a ligand...
May 25, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28498408/induction-of-il-17-production-from-human-peripheral-blood-cd4-cells-by-asbestos-exposure
#2
Megumi Maeda, Ying Chen, Suni Lee, Naoko Kumagai-Takei, Kei Yoshitome, Hidenori Matsuzaki, Shoko Yamamoto, Tamayo Hatayama, Miho Ikeda, Yasumitsu Nishimura, Takemi Otsuki
We have previously reported that chronic, recurrent and low-dose exposure to asbestos fibers causes a reduction in antitumor immunity. Investigation of natural killer (NK) cells using an in vitro cell line model and comprising in vitro activation using freshly isolated NK cells co-cultured with chrysotile fibers, as well as NK cells derived from asbestos-exposed patients with pleural plaque (PP) or malignant mesothelioma (MM), revealed decreased expression of NK cell activating receptors such as NKG2D, 2B4 and NKp46...
May 9, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28492360/resveratrol-inhibits-periodontitis-related-bone-loss-in-rats-submitted-to-cigarette-smoke-inhalation
#3
Fernanda V Ribeiro, Danilo S Pino, Felipe C Franck, Bruno B Benatti, Howard Tenenbaum, Dip Perio, John E Davies, Suzana P Pimentel, Renato C Casarin, Fabiano R Cirano, Marcio Z Casati
BACKGROUND: Alternative therapeutic approaches have been explored in order to modulate the host's response to periodontal disease. The knowledge of new strategies to treat periodontitis is particularly relevant in patients presenting augmented risk to periodontitis, as smokers. The aim of this study was to investigate the impact of Resveratrol (RESV) on the progression of experimental periodontitis (EP) in the presence of cigarette smoke inhalation (CSI). METHODS: Rats were assigned to: CSI+RESV(n=20); CSI+placebo(n=20); Non-CSI(n=20)...
May 11, 2017: Journal of Periodontology
https://www.readbyqxmd.com/read/28484461/blockade-of-neutrophil-s-chemokine-receptors-cxcr1-2-abrogate-liver-damage-in-acute-on-chronic-liver-failure
#4
Arshi Khanam, Nirupma Trehanpati, Peggy Riese, Archana Rastogi, Carlos Alberto Guzman, Shiv Kumar Sarin
BACKGROUND: Neutrophils serve as critical players in the pathogenesis of liver diseases. Chemokine receptors CXCR1 and CXCR2 are required for neutrophil chemotaxis to the site of inflammation/injury and are crucial in hepatic inflammatory response. However, key mechanism of neutrophil-mediated liver injury in acute-on-chronic liver failure (ACLF) remains highly elusive; which could be targeted for the development of new therapeutic interventions. METHODS: To demonstrate the role of CXCR1/CXCR2-expressing neutrophils in hepatic injury, we investigated CXCR1/CXCR2 receptor expression in 17 hepatitis B virus-related ACLF patients in comparison to 42 chronic hepatitis B and 18 healthy controls...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28482409/-protective-effect-of-glycogen-synthase-kinase-3%C3%AE-inhibition-via-peroxisome-proliferator-activated-receptor-alpha-activation-in-mice-with-acute-liver-failure
#5
H B Shi, H L Shi, X Y Zhang, D X Chen, Z P Duan, F Ren
Objective: To investigate the role of the glycogen synthase kinase 3β (GSK3β) and the peroxisome proliferator-activated receptor alpha (PPARα) signaling pathway in acute liver failure and related mechanisms in a mouse model of acute liver failure induced by D-galactosamine/lipopolysaccharide (D-GalN/LPS). Methods: C57BL/6 mice were given intraperitoneal injection of D-GalN/LPS to establish a mouse model of acute liver failure. SB216763 was used to inhibit the activity of GSK3β and PPARα siRNA was used to inhibit the expression of PPARα...
March 20, 2017: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
https://www.readbyqxmd.com/read/28445259/the-role-of-stat3-and-ahr-in-the-differentiation-of-cd4-t-cells-into-th17-and-treg-cells
#6
Xingxing Liu, Hui Hu, Heng Fan, Dongmei Zuo, Zhexing Shou, Yi Liao, Zhen Nan, Qing Tang
BACKGROUND: This study aimed to investigate the role of aryl hydrocarbon receptor (AhR) and STAT3 gene during the differentiation of cluster of differentiation (CD)4 T cells into T helper (Th)17 and T regulatory (Treg) cells. METHODS: First, CD4 T cells were isolated from the spleen of BALB/c mice. Then, stable CD4 T cells expressing STAT3 shRNA were constructed. CD4 T cells were assigned to one of the following treatments: Th17 group: antibodies against CD3 and CD28, 2...
April 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28424593/phospholipase-a2-of-peroxiredoxin-6-plays-a-critical-role-in-cerebral-ischemia-reperfusion-inflammatory-injury
#7
Yu Shanshan, Jiang Beibei, Tan Li, Gao Minna, Lei Shipeng, Peng Li, Zhao Yong
Microglia-mediated inflammation is an important step in the progression of cerebral ischemia/reperfusion injury and the associated production of receptors of immunomoudulation, including Toll-like receptors (TLRs). Peroxiredoxin 6 (Prdx6) has been demonstrated as the endogenous antioxidant protein for its peroxidase properties. However, the role of the independent phospholipase A2 (iPLA2) activity of Prdx6 in stroke has not been well studied. In this study, we evaluated whether blocking the calcium-iPLA2 activity of Prdx6 using siRNA and inhibitors (1-hexadecyl-3-(trifluoroethgl)-sn-glycerol-2 phosphomethanol, MJ33) would have a critical effect on inflammatory brain damage...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28421819/il-4-induces-the-il17rb-gene-transcription-in-monocytic-cells-with-coordinate-autocrine-il-25-signaling
#8
Nathaniel M Weathington, Shreya S Kanth, Qiaoke Gong, James Londino, Akihiko Hoji, Mauricio Rojas, John Trudeau, Sally Wenzel, Rama K Mallampalli
IL-25 and IL-4 signaling in the setting of infection or allergic responses can drive Type 2 inflammation. IL-25 requires the IL-17 receptor B (IL-17Rb) to mediate signaling through nuclear factor kappa B transcriptional activation. Despite the known coexistence of these two cytokines in the Type 2 inflammatory environment, collaborative signaling between the IL-4 and IL-25 axes is poorly explored. Here we demonstrate IL-4 induction of both IL-25 and IL-17Rb protein in human lung tissue culture, primary alveolar macrophages, and the THP-1 monocytic cell line...
April 19, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28415830/triptolide-mitigates-radiation-induced-pneumonitis-via-inhibition-of-alveolar-macrophages-and-related-inflammatory-molecules
#9
Chun Chen, Shanmin Yang, Mei Zhang, Zhenhuan Zhang, Steven B Zhang, Bing Wu, Jinsheng Hong, Weijian Zhang, Jianhua Lin, Paul Okunieff, Lurong Zhang
Ionizing radiation-induced pulmonary injury is a major limitation of radiotherapy for thoracic tumors. We have demonstrated that triptolide (TPL) could alleviate IR-induced pneumonia and pulmonary fibrosis. In this study, we explored the underlying mechanism by which TPL mitigates the effects of radiotoxicity. The results showed that:(1) Alveolar macrophages (AMs) were the primary inflammatory cells infiltrating irradiated lung tissues and were maintained at a high level for at least 17 days, which TPL could reduce by inhibiting of the production of macrophage inflammatory protein-2 (MIP-2) and its receptor CXCR2...
March 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28414140/shear-stress-inhibits-il-17a-mediated-induction-of-osteoclastogenesis-via-osteocyte-pathways
#10
Chongshan Liao, Tianfan Cheng, Shuai Wang, Chengfei Zhang, Lijian Jin, Yanqi Yang
Interleukin (IL)-17 is crucial to osteoclast differentiation and activation. Osteocytes support osteoclast formation and are thought to orchestrate bone remodeling in response to fluid flow. The contribution of IL-17 to osteocyte-related bone resorption remains unclear. Here, we used the osteocyte-like MLO-Y4 cell line to examine the role of IL-17 and fluid flow in osteoclastogenesis. It was the first time to demonstrate that IL-17A promoted MLO-Y4 cell proliferation, enhanced expression of receptor activator of nuclear factor κ-B ligand (RANKL) and tumor necrosis factor-α (TNF-α), and induced osteoclastogenesis when MLO-Y4 cells were co-cultured with bone marrow-derived macrophage (BMM) cells...
April 14, 2017: Bone
https://www.readbyqxmd.com/read/28380520/the-addition-of-protein-bound-amino-acids-in-low-protein-diets-improves-the-metabolic-and-immunological-characteristics-in-fifteen-to-thirty-five-kg-pigs
#11
L Q Che, X Peng, L Hu, C Wu, Q Xu, Z F Fang, Y Lin, S Y Xu, J Li, B Feng, G Tian, R N Zhang, H Sun, D Wu, D W Chen
This study was to evaluate the effects of supplementation of AA form (crystalline vs. protein bound) in low-protein diets on growth, metabolic, and immunological characteristics of pigs. A total of 80 barrows (PIC 327 × 1050; 15.57 ± 0.13 kg BW and 48 ± 2 d of age), housed in 4 pigs per pen with 5 pens per treatment, were assigned to 4 dietary treatments of 17, 15, and 13% CP and 13% CP plus casein for 28 d. The crystalline AA were supplemented to meet the requirement of indispensable AA in pigs. Results showed that pigs fed the 13% CP diet or the 13% CP plus casein diet had lower ( < 0...
March 2017: Journal of Animal Science
https://www.readbyqxmd.com/read/28373650/vitamin-d3-inhibits-micro-rna-17-92-to-promote-specific-immunotherapy-in-allergic-rhinitis
#12
Zhi-Jian Yu, Lu Zeng, Xiang-Qian Luo, Xiao-Rui Geng, Rui Xu, Kun Chen, Gui Yang, Xi Luo, Zhi-Qiang Liu, Zhi-Gang Liu, Da-Bo Liu, Ping-Chang Yang, Hua-Bin Li
It is recognized that T helper 2 (Th2) polarization plays a critical role in a large number of immune disorders. Yet, the remedies for reconciling the established Th2 polarization are still limited currently. Published data indicate that micro RNA-17-92 cluster is associated with the skewed immune response; 25 vitamin D3 (VD3) can regulate multiple bioactivities in the body. This study tests a hypothesis that VD3 facilitates the effect of specific immunotherapy (SIT) on Th2 response. We observed that treatment with either SIT or VD3 alleviated AR symptoms as well as reduced serum levels of specific IgE and T helper (Th) 2 cytokines, suppressed miR-19a (one of the members of the miR-17-92 cluster) and increased IL-10 in peripheral B cells, which was further improved in those AR patients treated with both SIT and VD3...
April 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28356385/rgc-32-promotes-th17-cell-differentiation-and-enhances-experimental-autoimmune-encephalomyelitis
#13
Violeta Rus, Vinh Nguyen, Alexandru Tatomir, Jason R Lees, Armugam P Mekala, Dallas Boodhoo, Cosmin A Tegla, Irina G Luzina, Paul A Antony, Cornelia D Cudrici, Tudor C Badea, Horea G Rus
Th17 cells play a critical role in autoimmune diseases, including multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis. Response gene to complement (RGC)-32 is a cell cycle regulator and a downstream target of TGF-β that mediates its profibrotic activity. In this study, we report that RGC-32 is preferentially upregulated during Th17 cell differentiation. RGC-32(-/-) mice have normal Th1, Th2, and regulatory T cell differentiation but show defective Th17 differentiation in vitro...
May 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28341898/functional-block-of-il-17-cytokine-promotes-bone-healing-by-augmenting-foxo1-and-atf4-activity-in-cortical-bone-defect-model
#14
M Dixit, K B Singh, R Prakash, D Singh
We determine the effect of interleukin (IL)-17 neutralizing antibody on new bone regeneration. Anti-IL-17 antibody promoted new bone regeneration in cortical bone defect model by augmenting FOXO1 and ATF4 activity thereby decreasing oxidative stress. Our study demonstrates the bone healing and regeneration potential of neutralizing IL-17antibody in osteoporotic fractures. INTRODUCTION: The immune system plays important role in the fracture healing process. However, fracture healing is prolonged in disorders associated with systemic inflammation...
March 24, 2017: Osteoporosis International
https://www.readbyqxmd.com/read/28319123/saccharomyces-boulardii-and-bacillus-subtilis-b10-modulate-tlrs-and-cytokines-expression-patterns-in-jejunum-and-ileum-of-broilers
#15
Imran Rashid Rajput, Huang Ying, Sun Yajing, Muhammad Asif Arain, Li Weifen, Li Ping, Dost Muhammad Bloch, Liu Wenhua
The present study was designed to evaluate the effects of Saccharomyces boulardii (Sb) and Bacillus subtilis B10 (Bs) on intestinal epithelial Toll like receptors (TLR), and Cytokine expression response to understand the intestinal epithelial innate immune mechanism in broilers. A total of 300 birds (Sanhuang broilers) were allotted into three groups (n = 100) and each divided into five replications (n = 20). Control group (Ctr) birds were fed basal diet, broilers in experimental groups received (1×108cfu/kg feed) Sb and Bs respectively in addition to basal diet for 72 days...
2017: PloS One
https://www.readbyqxmd.com/read/28294424/therapeutic-regulation-of-systemic-inflammation-in-xenograft-recipients
#16
Hayato Iwase, Hong Liu, Tao Li, Zhongquiang Zhang, Bingsi Gao, Hidetaka Hara, Martin Wijkstrom, Cassandra Long, Ryan Saari, David Ayares, David K C Cooper, Mohamed B Ezzelarab
Inflammation is known to preclude tolerance after transplantation. We have previously shown that systemic inflammation in xenograft recipients (SIXR) precedes activation of coagulation in the absence of T cell responses. Accordingly, SIXR may amplify innate and adaptive immune responses against xenografts after pig-to-primate xenotransplantation, even with efficient immunosuppressive therapy. We evaluated the impact of anti-inflammatory agents on pro-inflammatory cytokines and chemokines in pig artery patch and heart xenograft recipients...
March 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28289409/mitochondrial-dna-activates-the-nlrp3-inflammasome-and-predisposes-to-type-1-diabetes-in-murine-model
#17
Daniela Carlos, Frederico R C Costa, Camila A Pereira, Fernanda A Rocha, Juliana N U Yaochite, Gabriela G Oliveira, Fernando S Carneiro, Rita C Tostes, Simone G Ramos, Dario S Zamboni, Niels O S Camara, Bernhard Ryffel, João S Silva
Although a correlation between polymorphisms of NOD-like receptor family-pyrin domain containing 3 (NLRP3) and predisposition to type 1 diabetes (T1D) has been identified, the potential function and activation of the NLRP3 inflammasome in T1D have not been clarified. The present study shows that non-obese diabetic mice exhibited increased NLRP3, and pro-IL-1β gene expression in pancreatic lymph nodes (PLNs). Similar increases in gene expression of NLRP3, apoptosis associated speck like protein (ASC) and pro-IL-1β were induced by multiple low doses of streptozotocin (STZ) in C57BL/6 mice...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28286938/n-acetyl-l-cysteine-controls-osteoclastogenesis-through-regulating-th17-differentiation-and-rankl-in-rheumatoid-arthritis
#18
Hae-Rim Kim, Kyoung-Woon Kim, Bo-Mi Kim, Kyung-Ann Lee, Sang-Heon Lee
Background/Aims: This study aimed to determine the regulatory role of N-acetyl-l-cysteine (NAC), an antioxidant, in interleukin 17 (IL-17)-induced osteoclast differentiation in rheumatoid arthritis (RA). Methods: After RA synovial fibroblasts were stimulated by IL-17, the expression and production of receptor activator of nuclear factor κ-B ligand (RANKL) was determined by real-time polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA). Osteoclastogenesis was also determined after co-cultures of IL-17-stimulated RA synovial fibroblasts, Th17 cells and various concentrations of NAC with monocytes...
March 13, 2017: Korean Journal of Internal Medicine
https://www.readbyqxmd.com/read/28284343/sphk1-mediates-neuroinflammation-and-neuronal-injury-via-traf2-nf-%C3%AE%C2%BAb-pathways-in-activated-microglia-in-cerebral-ischemia-reperfusion
#19
Danying Su, Yuefeng Cheng, Shi Li, Dawei Dai, Wei Zhang, Manhua Lv
Sphingosine kinase 1 (Sphk1), a key enzyme responsible for phosphorylating sphingosine into sphingosine1-phosphate (S1P), plays an important role in mediating post-stroke neuroinflammation. However, the pathway and mechanism of the Sphk1-mediated inflammatory response remains unknown. In this study, we found that suppression of Sphk1 decreased IL17 production and relieved neuronal damage induced by microglia in cerebral ischemia reperfusion (IR) or in an in vitro oxygen-glucose deprivation reperfusion (OGDR) system...
April 15, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/28278201/the-symbiotic-bacterial-surface-factor-polysaccharide-a-on-bacteroides-fragilis-inhibits-il-1%C3%AE-induced-inflammation-in-human-fetal-enterocytes-via-toll-receptors-2-and-4
#20
Fei Jiang, Di Meng, Meiqian Weng, Weishu Zhu, Wenxue Wu, Dennis Kasper, W Allan Walker
Colonizing bacteria interacting with the immature, unlike the mature, human intestine favors inflammation over immune homeostasis. As a result, ten percent of premature infants under 1500 grams weight develop an inflammatory necrosis of the intestine after birth, e.g., necrotizing enterocolitis (NEC). NEC is a major health problem in this population causing extensive morbidity and mortality and an enormous expenditure of health care dollars. NEC can be prevented by giving preterm infants their mother's expressed breast milk or ingesting selective probiotic organisms...
2017: PloS One
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