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https://www.readbyqxmd.com/read/28433199/glycoprotein-non-metastatic-melanoma-protein-b-gpnmb-is-highly-expressed-in-macrophages-of-acute-injured-kidney-and-promotes-m2-macrophages-polarization
#1
Letian Zhou, Hui Zhuo, Huiyu Ouyang, Yexin Liu, Fang Yuan, Lin Sun, Fuyou Liu, Hong Liu
Acute kidney injury (AKI) is an increasingly common disorder that is strongly linked to short- and long-term morbidity and mortality. During AKI process, macrophages, one of the important immune response cells, can polarize into M1 and M2 subtype from M0 subtype. It is well-known that M1 macrophages play a pro inflammatory role while M2 macrophages play an anti-inflammatory role. Glycoprotein non-metastatic melanoma protein b (Gpnmb) is a glycosylated transmembrane protein highly expressed in numerous cells, including osteoblasts, dendritic cells and macrophages...
March 31, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28430601/growth-suppressive-activity-of-raloxifene-on-liver-cancer-cells-by-targeting-il-6-gp130-signaling
#2
Yina Wang, Haiyan Ma, Chongqiang Zhao, Tianshu Liu, Dan Yan, David Jou, Huameng Li, Cuntai Zhang, Jiagao Lü, Chenglong Li, Jiayuh Lin, Sheng Li, Li Lin
BACKGROUND: Interleukin-6 (IL-6) is a multifunctional cytokine, which is involved in the regulation of differentiation and growth of certain types of tumor cells. Constitutive activation of Signal Transducer and Activator of Transcription 3 (STAT3) induced by IL-6 is frequently detected in liver cancer and has emerged as a viable molecular target for liver cancer treatment. However, few inhibitors targeting up-streams of STAT3 are available for the therapy of liver cancer. We reported the discovery of EVISTA (Raloxifene HCl) as novel inhibitor of IL-6/GP130 protein-protein interactions (PPIs) using multiple ligand simultaneous docking (MLSD) and drug repositioning...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28421819/il-4-induces-the-il17rb-gene-transcription-in-monocytic-cells-with-coordinate-autocrine-il-25-signaling
#3
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/28420758/the-foxm1-inhibitor-rcm-1-suppresses-goblet-cell-metaplasia-and-prevents-il-13-and-stat6-signaling-in-allergen-exposed-mice
#4
Lifeng Sun, Xiaomeng Ren, I-Ching Wang, Arun Pradhan, Yufang Zhang, Hannah M Flood, Bo Han, Jeffrey A Whitsett, Tanya V Kalin, Vladimir V Kalinichenko
Goblet cell metaplasia and excessive mucus secretion associated with asthma, cystic fibrosis, and chronic obstructive pulmonary disease contribute to morbidity and mortality worldwide. We performed a high-throughput screen to identify small molecules targeting a transcriptional network critical for the differentiation of goblet cells in response to allergens. We identified RCM-1, a nontoxic small molecule that inhibited goblet cell metaplasia and excessive mucus production in mice after exposure to allergens...
April 18, 2017: Science Signaling
https://www.readbyqxmd.com/read/28420002/associations-between-stat-gene-polymorphisms-and-psoriasis-in-northeastern-china
#5
Jing Zhou, Yuzhen Li, Donglin Sun
BACKGROUND: Psoriasis is an autoimmune disease with genetic and environmental factors. Based on the roles of STATs (signaling transducers and activators of transcription) in autoimmune diseases, it is assumed STAT gene polymorphisms are associated with psoriasis. OBJECTIVES: To study the association between STAT gene polymorphisms and psoriasis in the northeastern Chinese population. METHODS: Eight single-nucleotide polymorphisms were genotyped: rs2293152, rs3816769, rs4796793, and rs744166 in STAT3, rs7574865 and rs3024866 in STAT4, and rs324011 and rs3024974 in STAT6, using SNaPshot methods...
April 19, 2017: Dermatology: International Journal for Clinical and Investigative Dermatology
https://www.readbyqxmd.com/read/28419526/soluble-egg-antigen-activates-m2-macrophages-via-the-stat6-and-pi3k-pathways-and-schistosoma-japonicum-alternatively-activates-macrophage-polarization-to-improve-the-survival-rate-of-septic-mice
#6
Hao Tang, Yan-Bing Liang, Zhi-Bin Chen, Lin-Lin Du, Li-Jin Zeng, Jing-Guo Wu, Wen Yang, Hua-Ping Liang, Zhong-Fu Ma
Sepsis is one of the most challenging health problems worldwide. Our previous study showed that chronic schistosoma japonica (SJ) infection might increase serum anti-inflammatory factors to play a protective role, thus improving the survival rate of septic mice. Further research revealed that SJ infection promoted J774A.1 macrophage differentiation into M2 macrophages; suppressed LPS-induced activation of M1 macrophages; up-regulated CD163, IL-10 and TGF-β1 expression; inhibited TNF-α and iNOS expression; and blocked the effect of LPS-promoted TNF-α and iNOS expression...
April 17, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28414040/sars-coronavirus-papain-like-protease-up-regulates-the-collagen-expression-through-non-samd-tgf-%C3%AE-1-signaling
#7
Ching-Ying Wang, Chien-Yi Lu, Shih-Wen Li, Chien-Chen Lai, Chun-Hung Hua, Su-Hua Huang, Ying-Ju Lin, Mann-Jen Hour, Cheng-Wen Lin
SARS coronavirus (CoV) papain-like protease (PLpro) reportedly induced the production of TGF-β1 through p38 MAPK/STAT3-meidated Egr-1-dependent activation (Sci. Rep. 6, 25754). This study investigated the correlation of PLpro-induced TGF-β1 with the expression of Type I collagen in human lung epithelial cells and mouse pulmonary tissues. Specific inhibitors for TGF-βRI, p38 MAPK, MEK, and STAT3 proved that SARS-CoV PLpro induced TGF-β1-dependent up-regulation of Type I collagen in vitro and in vivo. Subcellular localization analysis of SMAD3 and SMAD7 indicated that non-SMAD pathways in TGF-β1 signaling involved in the production of Type I collagen in transfected cells with pSARS-PLpro...
April 13, 2017: Virus Research
https://www.readbyqxmd.com/read/28410469/18%C3%AE-glycyrrhetinic-acid-the-major-bioactive-component-of-glycyrrhizae-radix-attenuates-airway-inflammation-by-modulating-th2-cytokines-gata-3-stat6-and-foxp3-transcription-factors-in-an-asthmatic-mouse-model
#8
Seung-Hyung Kim, Jung-Hee Hong, Ji-Eun Lee, Young-Cheol Lee
18β-Glycyrrhetinic acid (18Gly), the major bioactive component of Glycyrrhizae Radix, possesses anti-ulcerative, anti-inflammatory, and other pharmacological properties. Although 18Gly is associated with immunoregulatory functions of allergic diseases, the pathophysiological mechanisms of 18Gly action in allergic inflammatory lung disease have not been examined. Moreover, there are no in vivo studies on the anti-asthmatic effects of 18Gly in allergic asthma. We investigated its effect and mechanism of action in airway inflammation in a BALB/c mouse model of allergic asthma...
March 20, 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/28399411/inhibition-of-hematopoietic-cell-kinase-activity-suppresses-myeloid-cell-mediated-colon-cancer-progression
#9
Ashleigh R Poh, Christopher G Love, Frederick Masson, Adele Preaudet, Cary Tsui, Lachlan Whitehead, Simon Monard, Yelena Khakham, Lotta Burstroem, Guillaume Lessene, Oliver Sieber, Clifford Lowell, Tracy L Putoczki, Robert J J O'Donoghue, Matthias Ernst
Aberrant activation of the SRC family kinase hematopoietic cell kinase (HCK) triggers hematological malignancies as a tumor cell-intrinsic oncogene. Here we find that high HCK levels correlate with reduced survival of colorectal cancer patients. Likewise, increased Hck activity in mice promotes the growth of endogenous colonic malignancies and of human colorectal cancer cell xenografts. Furthermore, tumor-associated macrophages of the corresponding tumors show a pronounced alternatively activated endotype, which occurs independently of mature lymphocytes or of Stat6-dependent Th2 cytokine signaling...
April 10, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28385737/lack-of-stat6-attenuates-inflammation-and-drives-protection-against-early-steps-of-colitis-associated-colon-cancer
#10
Sonia A Leon-Cabrera, Emmanuel Molina-Guzman, Yael G Delgado-Ramirez, Armando Vázquez-Sandoval, Yadira Ledesma-Soto, Carlos G Pérez-Plasencia, Yolanda I Chirino, Norma L Delgado-Buenrostro, Miriam Rodríguez-Sosa, Felipe Vaca-Paniagua, Federico Ávila-Moreno, Emma B Gutierrez-Cirlos, Luis E Arias-Romero, Luis I Terrazas
Colitis-associated colon cancer (CAC) is one of the most common malignant neoplasms and a leading cause of death. The immunologic factors associated with CAC development are not completely understood. Signal transducer and activator of transcription 6 (STAT6) is part of an important signaling pathway for modulating intestinal immune function and homeostasis. However, the role of STAT6 in colon cancer progression is unclear. Following CAC induction in wild-type (WT) and STAT6-deficient mice (STAT6(-/-)), we found that 70% of STAT6(-/-) mice were tumor-free after 8 weeks, whereas 100% of WT mice developed tumors...
April 6, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28383559/erythropoietin-protects-against-rhabdomyolysis-induced-acute-kidney-injury-by-modulating-macrophage-polarization
#11
Shuo Wang, Chao Zhang, Jiawei Li, Sidikejiang Niyazi, Long Zheng, Ming Xu, Ruiming Rong, Cheng Yang, Tongyu Zhu
Erythropoietin (EPO) is a well-known hormone that is clinically used for the treatment of anemia. Very recently, an increasing body of evidence showed that EPO could still regulate bioactivities of macrophages. However, the details about the immunomodulatory effect of EPO on macrophages are not fully delineated, particularly in the setting of renal damages. Therefore, in the present study, we determined whether EPO could exert an impact on the dynamics of macrophages in a well-established model of rhabdomyolysis-induced acute kidney injury and explored the potential mechanisms...
April 6, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28376588/-expression-and-significance-of-stat6-in-solitary-fibrous-tumor
#12
Z Y Ding, Y F Wang, X Wang, Q Rao
Objective: To study the clinicopathologic features, the differential diagnosis and the expression of STAT6 in solitary fibrous tumor (SFT). Methods: Eighty cases of SFT were evaluated. The expression of STAT6, CD34, CD99 and bcl-2 protein was studied in these cases and in other groups of soft tissue tumors by immunohistochemical EnVision method. The results were analyzed and relevant literature were reviewed. Results: The expression rate of STAT6 in SFT was 97.5% (78/80) and that in other soft tissue tumors was 3...
April 8, 2017: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
https://www.readbyqxmd.com/read/28366783/intestinal-immune-responses-of-jian-carp-against-aeromonas-hydrophila-depressed-by-choline-deficiency-varied-change-patterns-of-mrna-levels-of-cytokines-tight-junction-proteins-and-related-signaling-molecules-among-three-intestinal-segments
#13
Pei Wu, Yang Liu, Wei-Dan Jiang, Jun Jiang, Yong-An Zhang, Xiao-Qiu Zhou, Lin Feng
This study aimed to investigate the effects of choline deficiency on intestinal inflammation of fish after Aeromonas hydrophila infection and the potential molecular mechanisms. Juvenile Jian carp (Cyprinus carpio var. Jian) were fed two diets containing choline at 165 (deficient group) and 607 mg/kg diet respectively for 65 days. Choline deficiency decreased intestinal lysozyme activity, C3 and IgM contents, increased acid phosphatase activity, downregulated mRNA levels of antimicrobial peptides [liver-expressed antimicrobial peptide (LEAP) 2A, LEAP-2B, hepcidin and defensin], cytokines [interleukin (IL) 6a, tumor necrosis factor α (TNF-α), interferon γ2b (IFN-γ2b), IL-6b and transforming growth factor β2 (TGF-β2) only in proximal intestine, IL-10 in mid and distal intestine], immune-related signaling molecules [Toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), nuclear factor kappa B (NF-κB), inhibitor of NF-κB (IκB), Janus kinase 3 (JAK3), and signal transducers and activators of transcription 5 (STAT5)], tight junction proteins (claudin 3b, claudin 3c, claudin 11 and occludin), and mitogen-activated protein kinases p38 (p38(MAPK)) in proximal and distal intestine of juvenile Jian carp after A...
March 30, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28365704/interleukin-4-induces-cpg-site-specific-demethylation-of-the-pendrin-promoter-in-primary-human-bronchial-epithelial-cells
#14
Giada Scantamburlo, Simone Vanoni, Silvia Dossena, Selma M Soyal, Emanuele Bernardinelli, Davide Antonio Civello, Wolfgang Patsch, Markus Paulmichl, Charity Nofziger
Pendrin is upregulated in bronchial epithelial cells following IL-4 stimulation via binding of STAT6 to an N4 GAS motif. Basal CpG methylation of the pendrin promoter is cell-specific. We studied if a correlation exists between IL-4 sensitivity and the CpG methylation status of the pendrin promoter in human bronchial epithelial cell models. METHODS: Real-time PCR and pyrosequencing were used to respectively quantify pendrin mRNA levels and methylation of pendrin promoter, with and without IL-4 stimulation, in healthy and diseased primary HBE cells, as well as NCI-H292 cells...
March 24, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28365359/leflunomide-prevents-ros-induced-systemic-fibrosis-in-mice
#15
Florence Morin, Niloufar Kavian, Sandrine Chouzenoux, Olivier Cerles, Carole Nicco, Christiane Chéreau, Frédéric Batteux
Systemic sclerosis (SSc) is a connective tissue disorder characterized by fibrosis of the skin and inner organs, vasculopathy and immunological abnormalities. Recent insights into the polarization of macrophages in scleroderma and into the implication of STAT6 and KLF4 in this process have prompted us to investigate the effects of the inhibition of STAT6 signaling pathway by leflunomide in mice. SSc was induced in BALB/c mice by daily subcutaneous injections of hypochlorous acid (HOCl) or bleomycin. Mice were treated (or not) every other day, for 4 or 6 weeks, by leflunomide...
March 30, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28363777/dual-genetic-absence-of-stat6-and-il-10-does-not-abrogate-anti-hyperglycemic-effects-of-schistosoma-mansoni-in-streptozotocin-treated-diabetic-mice
#16
Yoshio Osada, Tomohiro Fujiyama, Naoto Kamimura, Tsukushi Kaji, Susumu Nakae, Katsuko Sudo, Kenji Ishiwata, Tamotsu Kanazawa
Schistosoma mansoni (Sm) is known to exert protective effects against various allergic and autoimmune disorders. It has been reported that this parasite protects NOD mice from spontaneous type 1 diabetes (T1D) and ameliorates streptozotocin (STZ)-induced T1D in wild-type mice. Here, we tried to clarify the anti-diabetic mechanisms of Sm in the latter model. Sm infection partially prevented the degradation of pancreatic islets and hyperglycemia in multiple low-dose (MLD) STZ-treated mice. Neither Treg cell depletion nor genetic absences of IL-10 and/or STAT6 abrogated the anti-hyperglycemic effects of Sm...
March 28, 2017: Experimental Parasitology
https://www.readbyqxmd.com/read/28352104/helminth-induced-alterations-of-the-gut-microbiota-exacerbate-bacterial-colitis
#17
C Su, L Su, Y Li, S R Long, J Chang, W Zhang, W A Walker, R J Xavier, B J Cherayil, H N Shi
Infection with the intestinal helminth parasite Heligmosomoides polygyrus exacerbates the colitis caused by the bacterial enteropathogen Citrobacter rodentium. To clarify the underlying mechanism, we analyzed fecal microbiota composition of control and helminth-infected mice and evaluated the functional role of compositional differences by microbiota transplantation experiments. Our results showed that infection of Balb/c mice with H. polygyrus resulted in significant changes in the composition of the gut microbiota, characterized by a marked increase in the abundance of Bacteroidetes and decreases in Firmicutes and Lactobacillales...
March 29, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28351935/bidirectional-immune-tolerance-in-non-myeloablative-mhc-mismatched-bmt-for-murine-%C3%AE-thalassemia
#18
Shuyu E, Aman Seth, Peter Vogel, Matt Sommers, Taren Ong, Asha B Pillai
Non-myeloablative conditioning using total lymphoid irradiation (TLI) and rabbit anti-thymocyte serum (ATS) (the murine pre-clinical equivalent of anti-thymocyte globulin/ATG) facilitates immune tolerance after bone marrow transplantation (BMT) across major histocompatibility complex (MHC) disparities and may be a useful strategy for non-malignant disorders. We previously reported that donor effector T cell function and GVHD are regulated via recipient invariant natural killer T cell (iNKT cell) IL-4-driven expansion of donor Foxp3(+) naturally occurring Treg...
March 28, 2017: Blood
https://www.readbyqxmd.com/read/28348271/identification-of-novel-stat6-regulated-proteins-in-mouse-b-cells-by-comparative-transcriptome-and-proteome-analysis
#19
Lavanya Mokada-Gopal, Alexander Boeser, Christian H K Lehmann, Friedel Drepper, Diana Dudziak, Bettina Warscheid, David Voehringer
The transcription factor STAT6 plays a key role in mediating signaling downstream of the receptors for IL-4 and IL-13. In B cells, STAT6 is required for class switch recombination to IgE and for germinal center formation during type 2 immune responses directed against allergens or helminths. In this study, we compared the transcriptomes and proteomes of primary mouse B cells from wild-type and STAT6-deficient mice cultured for 4 d in the presence or absence of IL-4. Microarray analysis revealed that 214 mRNAs were upregulated and 149 were downregulated >3-fold by IL-4 in a STAT6-dependent manner...
March 27, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28340575/nox2-deficiency-alters-macrophage-phenotype-through-an-il-10-stat3-dependent-mechanism-implications-for-traumatic-brain-injury
#20
James P Barrett, Rebecca J Henry, Sonia Villapol, Bogdan A Stoica, Alok Kumar, Mark P Burns, Alan I Faden, David J Loane
BACKGROUND: NADPH oxidase (NOX2) is an enzyme system that generates reactive oxygen species (ROS) in microglia and macrophages. Excessive ROS production is linked with neuroinflammation and chronic neurodegeneration following traumatic brain injury (TBI). Redox signaling regulates macrophage/microglial phenotypic responses (pro-inflammatory versus anti-inflammatory), and NOX2 inhibition following moderate-to-severe TBI markedly reduces pro-inflammatory activation of macrophages/microglia resulting in concomitant increases in anti-inflammatory responses...
March 24, 2017: Journal of Neuroinflammation
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