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https://www.readbyqxmd.com/read/28433566/%C3%AE-aminoisobutyric-acid-ameliorates-the-renal-fibrosis-in-mouse-obstructed-kidneys-via-inhibition-of-renal-fibroblast-activation-and-fibrosis
#1
Huijuan Wang, Jun Qian, Xiufen Zhao, Changing Xing, Bin Sun
Renal fibrosis is a hallmark feature of chronic kidney disease, which is reflected by proliferation and migration of interstitial fibroblasts and extracellular matrix (ECM) accumulation. β-Aminoisobutyric acid (BAIBA) is recently demonstrated to exert a protective role from metabolic diseases. However, whether and how BAIBA on fibroblast activation and renal fibrosis response to angiotensin II (Ang II) remains largely obscure. Herein, we showed that BAIBA significantly depressed the proliferation and migration of NRK-49F cells in vitro...
February 8, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28433514/cox-2-inhibition-potentiates-mouse-bone-marrow-stem-cell-engraftment-and-differentiation-mediated-wound-repair
#2
Ramasatyaveni Geesala, Neha R Dhoke, Amitava Das
BACKGROUND: Engraftment of transplanted stem cells is often limited by cytokine and noncytokine proinflammatory mediators at the injury site. We examined the role of Cyclooxygenase-2 (Cox-2)-induced cytokine-mediated inflammation on engraftment of transplanted bone marrow stem cells (BMSCs) at the wound site. METHODS: BMSCs isolated from male C57/BL6J mice were transplanted onto excisional splinting wounds in syngenic females in presence or absence of celecoxib, Cox-2 specific inhibitor (50 mg/kg, body weight [b wt]), to evaluate engraftment and wound closure...
April 19, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28433154/non-immunogenic-porous-and-antibacterial-chitosan-and-antheraea-mylitta-silk-sericin-hydrogels-as-potential-dermal-substitute
#3
Sunaina Sapru, Ananta K Ghosh, Subhas C Kundu
Limitation of existing grafts including restricted donor site, risks of immune reactions, infectious diseases and high cost alarms the growing need of natural, cost effective and functional graft as the dermal substitute. We fabricate stable (>6 weeks) and porous (57.23-75.22μm) yet flexible (in variable pH) matrices using Antheraea mylitta sericin crosslinked with well known biocompatible polysaccharide chitosan by natural crosslinker (genipin) without using any harsh chemical. The fabricated matrices are characterized in terms of chemical modifications (Fourier transform infrared spectroscopy), crystallinity (X-ray diffraction), swelling, degradability and thermal stability...
July 1, 2017: Carbohydrate Polymers
https://www.readbyqxmd.com/read/28432149/cd73-on-t-cells-orchestrates-cardiac-wound-healing-after-myocardial-infarction-by-purinergic-metabolic-reprogramming
#4
Nadine Borg, Christina Alter, Nicole Görldt, Christoph Jacoby, Zhaoping Ding, Bodo Steckel, Christine Quast, Florian Bönner, Daniela Friebe, Sebastian Temme, Ulrich Flögel, Jürgen Schrader
Background -T-cells are required for proper healing after myocardial infarction. The mechanism of their beneficial action, however, is unknown. The pro-inflammatory "danger signal" adenosine triphosphate (ATP), released from damaged cells, is degraded by the ectonucleotidases CD39 and CD73 to the anti-inflammatory mediator adenosine. Here, we investigate the contribution of CD73-derived adenosine produced by T-cells to cardiac remodeling after ischemia/reperfusion and define its mechanism of action. Methods -Myocardial ischemia (50 min /reperfusion) was induced in global CD73(-/-) and CD4-CD73(-/-) mice...
April 21, 2017: Circulation
https://www.readbyqxmd.com/read/28431315/effects-of-pm2-5-exposure-on-the-notch-signaling-pathway-and-immune-imbalance-in-chronic-obstructive-pulmonary-disease
#5
Xing-Yu Gu, Xu Chu, Xiao-Li Zeng, Hai-Rong Bao, Xiao-Ju Liu
Chronic Obstructive Pulmonary Disease (COPD) is associated with T lymphocytes subset (Th1/Th2, Th17/Treg) imbalance. Notch signaling pathway plays a key role in the development of the adaptive immunity. The immune disorder induced by fine particulate matter (PM2.5) is related to COPD. The aim of this study was to investigate the mechanism by which PM2.5 influences the Notch signaling pathway leading to worsening immune disorder and accelerating COPD development. A COPD mouse model was established by cigarette smoke exposure...
April 18, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/28424593/phospholipase-a2-of-peroxiredoxin-6-plays-a-critical-role-in-cerebral-ischemia-reperfusion-inflammatory-injury
#6
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/28422756/%C3%AE-catenin-and-pi3k%C3%AE-inhibition-expands-precursor-th17-cells-with-heightened-stemness-and-antitumor-activity
#7
Kinga Majchrzak, Michelle H Nelson, Jacob S Bowers, Stefanie R Bailey, Megan M Wyatt, John M Wrangle, Mark P Rubinstein, Juan C Varela, Zihai Li, Richard A Himes, Sherine S L Chan, Chrystal M Paulos
ICOS costimulation generates Th17 cells with durable memory responses to tumor. Herein, we found that ICOS induces PI3K/p110δ/Akt and Wnt/β-catenin pathways in Th17 cells. Coinhibiting PI3Kδ and β-catenin altered the biological fate of Th17 cells. Th17 cells inhibited of both pathways expressed less RORγt, which, in turn, reduced their ability to secrete IL-17. Unexpectedly, these cells were more effective (than uninhibited cells) at regressing tumor when infused into mice, leading to long-term curative responses...
April 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28422002/treatment-of-psoriasis-with-ustekinumab-improved-skin-tightening-in-systemic-sclerosis
#8
Asako Ichihara, Masatoshi Jinnin, Hironobu Ihn
Systemic sclerosis (SSc) is a chronic autoimmune disease characterised by fibrosis, inflammation and vasculopathy in the skin and internal organs. Recently, several articles described that Th17 cells, IL-23 and IL-17 levels were significantly elevated in the peripheral blood or fibrotic sites of SSc. We report a case of SSc and psoriasis administered ustekinumab, IL-12/IL-23 inhibitor. In this case, the skin tightening was successfully improved and ustekinumab was more effective, even though oral prednisolone (9-12 mg/day) had some effect on skin tightening and arthralgia...
April 19, 2017: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/28420461/-%C3%AE-7-nicotinic-acetylcholine-receptor-agonist-attenuated-the-lipopolysaccharide-induced-inflammatory-response-via-inhibiting-the-activation-of-nuclear-factor-%C3%AE-b
#9
Xingxing Shi, Jianhua Yao, Cheng Wang, Xijing Zhang
OBJECTIVE: To investigate the effects of α7 nicotinic acetylcholine receptor (α7nAChR) on the inflammatory response induced by lipopolysaccharide (LPS) in RAW264.7 macrophages and its molecular mechanisms. METHODS: RAW264.7 macrophages were cultured in vitro. Inflammatory cell model was constructed by LPS stimulation. Cells were challenged by LPS (1, 10, 100 and 500 μg/L) for 5 hours or 100 μg/L LPS for 0, 2, 4, 8, 12, 24, 48 and 72 hours, and the release of tumor necrosis factor-α (TNF-α) was detected by the enzyme linked immunosorbent assay (ELISA)...
April 2017: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
https://www.readbyqxmd.com/read/28415830/triptolide-mitigates-radiation-induced-pneumonitis-via-inhibition-of-alveolar-macrophages-and-related-inflammatory-molecules
#10
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
#11
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/28411045/pro-inflammatory-effects-of-the-th1-chemokine-cxcl10-in-acquired-aplastic-anaemia
#12
Junhong Li, Meili Ge, Shihong Lu, Jun Shi, Xingxin Li, Min Wang, Jinbo Huang, Yingqi Shao, Zhendong Huang, Jing Zhang, Neng Nie, Yizhou Zheng
CXCL10/IFN-γ-induced protein 10 (IP-10) and its corresponding receptor CXCR3 have long been considered to be involved in the pathophysiology of type 1 T (Th1) cell-orientated autoimmune diseases. However, the exact role of CXCL10 in the pathogenesis of aplastic anaemia (AA) has not been thoroughly studied. The aim of our study was to evaluate the plasma level of CXCL10 and its effects on CD4(+) T cell differentiation in AA. In our study, we found that an elevated plasma level of CXCL10 was negatively correlated with platelet, absolute neutrophil and reticulocyte counts, while it was positively correlated with the proportion of lymphocytes in white blood cells in AA patients...
April 11, 2017: Cytokine
https://www.readbyqxmd.com/read/28407375/h19-promotes-cholestatic-liver-fibrosis-by-preventing-zeb1-mediated-inhibition-of-epcam
#13
Yongfeng Song, Chune Liu, Xia Liu, Jocelyn Trottier, Michele Beaudoin, Li Zhang, Chad Pope, Guangyong Peng, Olivier Barbier, Xiaobo Zhong, Linheng Li, Li Wang
Based on our recent finding that disruption of bile acid (BA) homeostasis in mice results in the induction of hepatic lncRNA H19 expression, we sought to elucidate the role of H19 in cholestatic liver fibrosis. Hepatic overexpression of H19RNA augmented bile duct ligation (BDL)-induced liver fibrosis, which was accompanied by the elevation of serum ALT, AST, bilirubin, and BA levels. Multiple genes related to liver fibrosis, inflammation, and biliary hyperplasia were increased in H19-BDL vs Null-BDL mice, whereas genes in BA synthesis were decreased...
April 13, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28404635/a-novel-mir-24-tcf1-axis-in-modulating-effector-t-cell-responses
#14
Sunglim Cho, Cheng-Jang Wu, Duc T Nguyen, Ling-Li Lin, Mei-Chi Chen, Aly Azeem Khan, Bi-Huei Yang, Wenxian Fu, Li-Fan Lu
miR-23∼27∼24 was recently implicated in restricting Th2 immunity, as well as the differentiation and function of other effector T cell lineages. Interestingly, miR-24, unlike other family members, actually promotes Th1 and Th17 responses. In this article, we show that miR-24 drives the production of IFN-γ and IL-17 in T cells at least in part through targeting TCF1, a transcription factor known for its role in limiting Th1 and Th17 immunity. Surprisingly, whereas TCF1 was previously shown to promote Th2 responses through inducing GATA3, enforced TCF1 expression in miR-24-overexpressing T cells led to further downregulation of IL-4 and GATA3 expression, suggesting miR-24-mediated inhibition of Th2 immunity cannot be attributed to TCF1 repression by miR-24...
April 12, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28400721/mir-384-regulates-the-th17-treg-ratio-during-experimental-autoimmune-encephalomyelitis-pathogenesis
#15
Xuebin Qu, Jingjing Han, Ying Zhang, Yuanyuan Wang, Jun Zhou, Hongbin Fan, Ruiqin Yao
Specific miRNAs are involved in the pathogenesis of multiple sclerosis (MS), during which IL-17-producing CD4(+) T helper (Th17) cells accumulate in the central nervous system (CNS). In this study, we identified levels of miR-384 as significantly increased in mice with experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Over-expression of miR-384 in vivo led to severe EAE, characterized by exacerbated demyelination, and increased inflammatory cell infiltration of the spinal cord; inhibition of miR-384 reversed these changes...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28399782/the-effects-of-chrysophanol-on-ovalbumin-ova-induced-chronic-lung-toxicology-by-inhibiting-th17-response
#16
Chunyan Zhang, Yafan Song, Congxia Wang, Ling Zhao, Huafeng Kang, Xiaobin Ma, Jing Wang, Tianzhu Zhang, Wang Shumin, Chunhua Ma
Chrysophanol (CH), extracted from plants of Rheum genus, possesses various pharmacological effects including anti-inflammatory activity. The purpose of the present study was to evaluate the protective effects and the underlying mechanisms of CH on ovalbumin (OVA)-induced asthma in mice. Fifty mice were randomly assigned to five experimental groups: control group, model group, dexamethasone (2 mg/kg) group and CH (5 and 10 mg/kg) groups. The number of eosinophil cells and the production of interleukin-6 (IL-6), IL-1β, IL-17 A and tumor necrosis factor-α in bronchoalveolar lavage fluid (BALF) were measured...
June 2017: Toxicology Mechanisms and Methods
https://www.readbyqxmd.com/read/28398870/interleukin-35-rescues-regulatory-b-cell-function-but-the-effect-is-dysregulated-in-ulcerative-colitis
#17
Shaoxuan Wang, Chengyong Qin
Ulcerative colitis (UC) is a long-time inflammatory condition arising from aberrant immune activation in the colon and the rectum. Interleukin (IL)-35 plays critical roles in autoimmune disorders. In this study, we explored the pathways of IL-35 in affecting UC. First, peripheral blood mononuclear cells (PBMCs) from UC patients were obtained. Pretreating PBMCs with IL-35 resulted in significantly elevated IL-10 production from whole PBMCs as well as B cells, whereas pretreating PBMCs with IL-12 or IL-27 did not demonstrate a similar effect...
February 16, 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/28389592/cutting-edge-selective-oral-rock2-inhibitor-reduces-clinical-scores-in-patients-with-psoriasis-vulgaris-and-normalizes-skin-pathology-via-concurrent-regulation-of-il-17-and-il-10
#18
Alexandra Zanin-Zhorov, Jonathan M Weiss, Alissa Trzeciak, Wei Chen, Jingya Zhang, Melanie S Nyuydzefe, Carmen Arencibia, Seetharam Polimera, Olivier Schueller, Judilyn Fuentes-Duculan, Kathleen M Bonifacio, Norma Kunjravia, Inna Cueto, Jennifer Soung, Roy M Fleischmann, Alan Kivitz, Mark Lebwohl, Margarita Nunez, Johnnie Woodson, Shondra L Smith, Robert F West, Mark Berger, James G Krueger, John L Ryan, Samuel D Waksal
Targeted inhibition of Rho-associated kinase (ROCK)2 downregulates the proinflammatory T cell response while increasing the regulatory arm of the immune response in animals models of autoimmunity and Th17-skewing human cell culture in vitro. In this study, we report that oral administration of a selective ROCK2 inhibitor, KD025, reduces psoriasis area and severity index scores by 50% from baseline in 46% of patients with psoriasis vulgaris, and it decreases epidermal thickness as well as T cell infiltration in the skin...
April 7, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28387597/human-cd39-treg-cells-express-th17-associated-surface-markers-and-suppress-il-17-via-a-stat3-dependent-mechanism
#19
Jessica R Magid-Bernstein, Christine M Rohowsky-Kochan
Human CD4(+) T regulatory cells (Tregs) are a population of phenotypically and functionally diverse cells that downregulate inflammatory and autoimmune responses. As Th17 cells play an important role in the pathogenesis of autoimmune diseases, it is critical to elucidate the mechanisms regulating these cells. In this study, we examined the molecular basis underlying the phenotypic and functional diversity of human Tregs expressing the ectonucleotidase CD39. CD4(+)CD25(hi)CD39(+) Tregs inhibit the proliferative response and the secretion of IL-17 and IFN-γ of autologous CD4(+) T effector cells, while CD4(+)CD25(hi)CD39(-) Tregs only suppress IFN-γ production...
April 2017: Journal of Interferon & Cytokine Research
https://www.readbyqxmd.com/read/28382171/hdac6-regulates-il-17-expression-in-t-lymphocytes-implications-for-hdac6-targeted-therapies
#20
Bing Yan, Yang Liu, Hong Bai, Miao Chen, Songbo Xie, Dengwen Li, Min Liu, Jun Zhou
The pro-inflammatory cytokine interleukin 17 (IL-17) is critically involved in immunity and inflammation. T-helper 17 and γδ T cells are the predominant sources of IL-17 in the immune system. However, the mechanisms by which the expression of IL-17 is regulated in T cells remain elusive. Here, we demonstrate that loss of histone deacetylase 6 (HDAC6) in mice does not affect the generation of CD4(+) or CD8(+) T cells, but stimulates the development of IL-17-producing γδ T cells. Our data further show that HDAC6 deficiency increases the production of IL-17 by Vγ4(+) γδ T cells in the spleen and lymph nodes...
2017: Theranostics
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