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https://www.readbyqxmd.com/read/28103257/activation-of-the-jak-stat-signaling-pathway-after-in-vitro-stimulation-with-ifn%C3%A3-in-multiple-sclerosis-patients-according-to-the-therapeutic-response-to-ifn%C3%A3
#1
Isaac Hurtado-Guerrero, Maria Jesús Pinto-Medel, Patricia Urbaneja, Jose Luis Rodriguez-Bada, Antonio León, Miguel Guerrero, Óscar Fernández, Laura Leyva, Begoña Oliver-Martos
Interferon beta (IFNß) is a common treatment used for multiple sclerosis (MS) which acts through the activation of the JAK-STAT pathway. However, this therapy is not always effective and currently there are no reliable biomarkers to predict therapeutic response. We postulate that the heterogeneity in the response to IFNß therapy could be related to differential activation patterns of the JAK-STAT signaling pathway. Our aim was to evaluate the basal levels and the short term activation of this pathway after IFNß stimulation in untreated and IFNß treated patients, as well as according to therapeutic response...
2017: PloS One
https://www.readbyqxmd.com/read/28102193/tumour-derived-interleukin-35-promotes-pancreatic-ductal-adenocarcinoma-cell-extravasation-and-metastasis-by-inducing-icam1-expression
#2
Chongbiao Huang, Na Li, Zengxun Li, Antao Chang, Yanan Chen, Tiansuo Zhao, Yang Li, Xiuchao Wang, Wei Zhang, Zhimin Wang, Lin Luo, Jingjing Shi, Shengyu Yang, He Ren, Jihui Hao
Interleukin 35 (IL-35) is a novel member of the IL-12 family, consisting of an EBV-induced gene 3 (EBI3) subunit and a P35 subunit. IL-35 is an immune-suppressive cytokine mainly produced by regulatory T cells. However, the role of IL-35 in cancer metastasis and progression is not well understood. Here we demonstrate that IL-35 is overexpressed in human pancreatic ductal adenocarcinoma (PDAC) tissues, and that IL-35 overexpression is associated with poor prognosis in PDAC patients. IL-35 has critical roles in PDAC cell extravasation and metastasis by facilitating the adhesion to endothelial cells and transendothelial extravasation...
January 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28101184/anti-inflammatory-effects-of-luteolin-on-experimental-autoimmune-thyroiditis-in-mice
#3
Nan Xia, Gang Chen, Min Liu, Xiaozhen Ye, Yahui Pan, Jiuyu Ge, Yanting Mao, Hongwei Wang, Jian Wang, Sijing Xie
Hashimoto's thyroiditis (HT) is the most common organ-specific autoimmune disease and is believed to be a predominately T cell-mediated autoimmunity. Signal transducer and activator of transcription (STAT)3 is a crucial transcription factor of T cell-mediated immunity, with key roles in the proliferation and migration of T helper (Th) cells, differentiation of Th cells into Th17 cells, and the balance between Treg cells and Th17 cells. Flavonoid luteolin has been shown to markedly inhibit Tyr705 activation/phosphorylation of STAT3 and exert anti-inflammatory effects in multiple sclerosis...
December 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28099902/anthelmintic-mebendazole-enhances-cisplatin-s-effect-on-suppressing-cell-proliferation-and-promotes-differentiation-of-head-and-neck-squamous-cell-carcinoma-hnscc
#4
Fugui Zhang, Yong Li, Hongmei Zhang, Enyi Huang, Lina Gao, Wenping Luo, Qiang Wei, Jiaming Fan, Dongzhe Song, Junyi Liao, Yulong Zou, Feng Liu, Jianxiang Liu, Jiayi Huang, Dan Guo, Chao Ma, Xue Hu, Li Li, Xiangyang Qu, Liqun Chen, Xinyi Yu, Zhicai Zhang, Tingting Wu, Hue H Luu, Rex C Haydon, Jinlin Song, Tong-Chuan He, Ping Ji
Head and neck squamous cell carcinoma (HNSCC) is one of the most common and aggressive types of human cancers worldwide. Nearly a half of HNSCC patients experience recurrence within five years of treatment and develop resistance to chemotherapy. Thus, there is an urgent clinical need to develop safe and novel anticancer therapies for HNSCC. Here, we investigate the possibility of repurposing the anthelmintic drug mebendazole (MBZ) as an anti-HNSCC agent. Using the two commonly-used human HNSCC lines CAL27 and SCC15, we demonstrate MBZ exerts more potent anti-proliferation activity than cisplatin in human HNSCC cells...
January 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28094337/glatiramer-acetate-attenuates-the-activation-of-cd4-t-cells-by-modulating-stat1-and-3-signaling-in-glia
#5
Ye-Hyeon Ahn, Sae-Bom Jeon, Chi Young Chang, Eun-Ah Goh, Sang Soo Kim, Ho Jin Kim, Jaewhan Song, Eun Jung Park
Interactions between immune effector cells of the central nervous system appear to directly or indirectly influence the progress/regression of multiple sclerosis (MS). Here, we report that glial STAT1 and -3 are distinctively phosphorylated following the interaction of activated lymphocytes and glia, and this effect is significantly inhibited by glatiramer acetate (GA), a disease-modifying drug for MS. GA also reduces the activations of STAT1 and -3 by MS-associated stimuli such as IFNγ or LPS in primary glia, but not neurons...
January 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28090315/chronic-mucocutaneous-candidiasis-disease-associated-with-inborn-errors-of-il-17-immunity
#6
REVIEW
Satoshi Okada, Anne Puel, Jean-Laurent Casanova, Masao Kobayashi
Chronic mucocutaneous candidiasis (CMC) is characterized by recurrent or persistent infections affecting the nails, skin and oral and genital mucosae caused by Candida spp., mainly Candida albicans. CMC is an infectious phenotype in patients with inherited or acquired T-cell deficiency. Patients with autosomal-dominant (AD) hyper IgE syndrome (HIES), AD signal transducer and activator of transcription 1 (STAT1) gain-of-function, autosomal-recessive (AR) deficiencies in interleukin (IL)-12 receptor β1 (IL-12Rβ1), IL-12p40, caspase recruitment domain-containing protein 9 (CARD9) or retinoic acid-related orphan receptor γT (RORγT) or AR autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) develop CMC as a major infectious phenotype that is categorized as Syndromic CMC...
December 2016: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28089769/nuclear-translocation-of-stat3-and-nf-%C3%AE%C2%BAb-are-independent-of-each-other-but-nf-%C3%AE%C2%BAb-supports-expression-and-activation-of-stat3
#7
Antons Martincuks, Katarzyna Andryka, Andrea Küster, Hildegard Schmitz-Van de Leur, Michal Komorowski, Gerhard Müller-Newen
NF-κB and STAT3 are essential transcription factors in immunity and act at the interface of the transition from chronic inflammation to cancer. Different functional crosstalks between NF-κB and STAT3 have been recently described arguing for a direct interaction of both proteins. During a systematic analysis of NF-κB/STAT3 crosstalk we observed that appearance of the subcellular distribution of NF-κB and STAT3 in immunofluorescence heavily depends on the fixation procedure. Therefore, we established an optimized fixation protocol for the reliable simultaneous analysis of the subcellular distributions of both transcription factors...
January 9, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28087906/-effect-and-its-molecular-mechanisms-of-curcumin-on-pulmonary-artery-smooth-muscle-cells-in-rat-model-with-chronic-obstructive-pulmonary-disease
#8
Xiangang Lin, Yenong Chen, Zhuqing Liu
Objective: To investigate the effects and the underlying molecular mechanisms of curcumin on pulmonary artery smooth muscle cells in rat model with chronic obstructive pulmonary disease (COPD). Methods: A total of 75 male Wistar rats were randomly divided into control group (group CN), model group (group M), low-dose curcumin group (group CL), medium-dose curcumin group (group CM) and high-dose curcumin group (group CH). HE staining was used to observe the morphology of pulmonary artery. Proliferating cell nuclear antigen (PCNA), apoptosis-related protein Bcl-2 and Bax were detected by immunohistochemical staining...
May 25, 2016: Zhejiang da Xue Xue Bao. Yi Xue Ban, Journal of Zhejiang University. Medical Sciences
https://www.readbyqxmd.com/read/28077577/extracellular-microrna-signature-of-human-helper-t-cell-subsets-in-health-and-autoimmunity
#9
Anna Torri, Donatella Carpi, Elisabetta Bulgheroni, Maria-Cristina Crosti, Monica Moro, Paola Gruarin, Riccardo L Rossi, Grazisa Rossetti, Dolores Di Vizio, Mirjam Hoxha, Valentina Bollati, Cristina Gagliani, Carlo Tacchetti, Moira Paroni, Jens Geginat, Laura Corti, Luigia Venegoni, Emilio Berti, Massimiliano Pagani, Giuseppe Matarese, Sergio Abrignani, Paola de Candia
Upon TCR stimulation, CD4+ T lymphocytes release extracellular vesicles (EVs) containing microRNAs. However, no data are available on whether human CD4+ T cell subsets release EVs containing different pattern of microRNAs. The present work aimed at filling this gap by assessing the microRNA content in EVs released upon in vitro TCR stimulation of Th1, Th17 and T regulatory (Treg) cells. Our results indicate that EVs released by Treg cells are significantly different compared to those released by the other subsets...
January 11, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28074916/corrigendum-il-17-promotes-angiogenic-factors-il-6-il-8-and-vegf-production-via-stat1-in-lung-adenocarcinoma
#10
Qi Huang, Iimin Duan, Xin Qian, Jinshuo Fan, Zhilei Lv, Xiuxiu Zhang, Jieli Han, Feng Wu, Mengfei Guo, Guorong Hu, Jiao Du, Caiyun Chen, Yang Jin
No abstract text is available yet for this article.
January 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28069953/c-type-lectin-receptor-dcir-modulates-immunity-to-tuberculosis-by-sustaining-type-i-interferon-signaling-in-dendritic-cells
#11
Anthony Troegeler, Ingrid Mercier, Céline Cougoule, Danilo Pietretti, André Colom, Carine Duval, Thien-Phong Vu Manh, Florence Capilla, Renaud Poincloux, Karine Pingris, Jérôme Nigou, Jörg Rademann, Marc Dalod, Frank A W Verreck, Talal Al Saati, Geanncarlo Lugo-Villarino, Bernd Lepenies, Denis Hudrisier, Olivier Neyrolles
Immune response against pathogens is a tightly regulated process that must ensure microbial control while preserving integrity of the infected organs. Tuberculosis (TB) is a paramount example of a chronic infection in which antimicrobial immunity is protective in the vast majority of infected individuals but can become detrimental if not finely tuned. Here, we report that C-type lectin dendritic cell (DC) immunoreceptor (DCIR), a key component in DC homeostasis, is required to modulate lung inflammation and bacterial burden in TB...
January 9, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28069426/impaired-nk-cell-functions-in-patients-with-stat1-gain-of-function-mutations
#12
Giovanna Tabellini, Donatella Vairo, Omar Scomodon, Nicola Tamassia, Rosalba Monica Ferraro, Ornella Patrizi, Sara Gasperini, Annarosa Soresina, Giuliana Giardino, Claudio Pignata, Vassilios Lougaris, Alessandro Plebani, Laura Dotta, Marco A Cassatella, Silvia Parolini, Raffaele Badolato
BACKGROUND: Gain-of-function (GOF) mutations affecting the coiled-coil domain or the DNA-binding domain of the Signal Transducer and Activator of Transcription 1 (STAT1) cause chronic mucocutaneous candidiasis disease (CMCD). This condition is characterized by fungal and bacterial infections due to impaired generation of Th17 cells; meanwhile some CMCD patients may also develop viral or intracellular pathogens infections. OBJECTIVE: To Investigate the effect of GOF-STAT1 mutations on functioning of Natural Killer (NK) cells...
January 6, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28069291/antagonizing-cytokine-mediated-jak-stat-signaling-by-porcine-reproductive-and-respiratory-syndrome-virus
#13
REVIEW
Liping Yang, Yan-Jin Zhang
Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway is activated by myriad cytokines, which are involved in regulation of cell growth, proliferation, differentiation, apoptosis, angiogenesis, immunity and inflammatory response. Because of its significance in immune response, JAK-STAT pathway is often targeted by pathogens, including porcine reproductive and respiratory syndrome virus (PRRSV). PRRSV causes reproductive failure in sows and respiratory disease in pigs of all ages...
December 30, 2016: Veterinary Microbiology
https://www.readbyqxmd.com/read/28065940/cd24-aggravates-acute-liver-injury-in-autoimmune-hepatitis-by-promoting-ifn-%C3%AE-production-by-cd4-t-cells
#14
Chenhong Zheng, Shulei Yin, Yang Yang, Yizhi Yu, Xiaohua Xie
The T-cell-mediated immune response is implicated in many clinical hepatic injuries, such as autoimmune hepatitis and acute virus hepatitis. CD24 is widely expressed by different immune cells and plays an important role in the pathogenesis of many autoimmune diseases. However, the role of CD24 in T-cell-mediated liver injury has not been elucidated until now. Here we showed that CD24 deficiency protects mice from concanavalin A (ConA)-induced fulminant liver injury by reducing serum interferon-γ (IFN-γ) levels...
January 9, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28064541/the-role-of-ifi35-in-lupus-nephritis-and-related-mechanisms
#15
Lihua Zhang, Honglin Zhu, Yisha Li, Xiaodan Dai, Bin Zhou, Quanzhen Li, Xiaoxia Zuo, Hui Luo
OBJECTIVES: It's reported that multiple genes in the IFN-γ/STAT1 pathway were hypomethylated and associated with the pathogenesis of lupus nephritis (LN). Our previous study using microarray analysis suggested that interferon induced 35-kDa protein (IFI35) was hypomethylated and increased in LN. However, the role of IFI35 in LN and related mechanism remains to be elucidate. METHODS: The expressions of IFNγR, STAT1, IFI35 and MBD2 in the human kidneys tissues was detected by real-time PCR and western blot...
January 9, 2017: Modern Rheumatology
https://www.readbyqxmd.com/read/28063793/interleukin-6-increases-the-expression-of-key-proteins-associated-with-steroidogenesis-in-human-nci-h295r-adrenocortical-cells
#16
Janae Strickland, Stephen McIlmoil, Brice J Williams, Dennis C Seager, James P Porter, Allan M Judd
Mechanisms of interleukin-6 (IL-6)-induced cortisol release (CR) were investigated by exposing H295R cells to IL-6 and determining mRNA/protein expression (PCR/western blots) for steroidogenic enzymes (SE), steroidogenic acute regulatory protein (StAR), steroidogenic factor-1 (SF-1)(enhances SE/StAR expression), activator protein 1 (AP-1)(regulates SE/StAR expression) and adrenal hypoplasia congenita-like protein (DAX-1)(inhibits SE/StAR expression). Promoter activity of StAR (SPA) was measured by a luciferase-coupled promoter...
January 4, 2017: Steroids
https://www.readbyqxmd.com/read/28062696/prostaglandin-e2-inhibition-of-il-27-production-in-murine-dendritic-cells-a-novel-mechanism-that-involves-irf1
#17
Kirsten M Hooper, Jui-Hung Yen, Weimin Kong, Kate M Rahbari, Ping-Chang Kuo, Ana M Gamero, Doina Ganea
IL-27, a multifunctional cytokine produced by APCs, antagonizes inflammation by affecting conventional dendritic cells (cDC), inducing IL-10, and promoting development of regulatory Tr1 cells. Although the mechanisms involved in IL-27 induction are well studied, much less is known about the factors that negatively impact IL-27 expression. PGE2, a major immunomodulatory prostanoid, acts as a proinflammatory agent in several models of inflammatory/autoimmune disease, promoting primarily Th17 development and function...
January 6, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28059079/trim14-is-a-putative-tumor-suppressor-and-regulator-of-innate-immune-response-in-non-small-cell-lung-cancer
#18
Josephine Hai, Chang-Qi Zhu, Tao Wang, Shawna L Organ, Frances A Shepherd, Ming-Sound Tsao
Non-small-cell lung carcinoma (NSCLC) accounts for 85% of malignant lung tumors and is the leading cause of cancer deaths. Our group previously identified Tripartite Motif 14 (TRIM14) as a component of a prognostic multigene expression signature for NSCLC. Little is known about the function of TRIM14 protein in normal or disease states. We investigated the functional and prognostic role of TRIM14 in NSCLC using in vitro and in vivo perturbation model systems. Firstly, a pooled RNAi screen identified TRIM14 to effect cell proliferation/survival in NSCLC cells...
January 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28051144/deep-transcriptomic-profiling-of-m1-macrophages-lacking-trpc3
#19
Sivarajan Kumarasamy, Sumeet Solanki, Oluwatomisin T Atolagbe, Bina Joe, Lutz Birnbaumer, Guillermo Vazquez
In previous studies using mice with macrophage-specific loss of TRPC3 we found a significant, selective effect of TRPC3 on the biology of M1, or inflammatory macrophages. Whereas activation of some components of the unfolded protein response and the pro-apoptotic mediators CamkII and Stat1 was impaired in Trpc3-deficient M1 cells, gathering insight about other molecular signatures within macrophages that might be affected by Trpc3 expression requires an alternative approach. In the present study we conducted RNA-seq analysis to interrogate the transcriptome of M1 macrophages derived from mice with macrophage-specific loss of TRPC3 and their littermate controls...
January 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28045028/chlorogenic-acid-inhibits-glioblastoma-growth-through-repolarizating-macrophage-from-m2-to-m1-phenotype
#20
Nina Xue, Qin Zhou, Ming Ji, Jing Jin, Fangfang Lai, Ju Chen, Mengtian Zhang, Jing Jia, Huarong Yang, Jie Zhang, Wenbin Li, Jiandong Jiang, Xiaoguang Chen
Glioblastoma is an aggressive tumor that is associated with distinctive infiltrating microglia/macrophages populations. Previous studies demonstrated that chlorogenic acid (5-caffeoylquinic acid, CHA), a phenolic compound with low molecular weight, has an anti-tumor effect in multiple malignant tumors. In the present study, we focused on the macrophage polarization to investigate the molecular mechanisms behind the anti-glioma response of CHA in vitro and in vivo. We found that CHA treatment increased the expression of M1 markers induced by LPS/IFNγ, including iNOS, MHC II (I-A/I-E subregions) and CD11c, and reduced the expression of M2 markers Arg and CD206 induced by IL-4, resulting in promoting the production of apoptotic-like cancer cells and inhibiting the growth of tumor cells by co-culture experiments...
January 3, 2017: Scientific Reports
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