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Cytokine signal transduction

Chengyong Lei, Shidong Lv, Hongyi Wang, Chuan Liu, Qiliang Zhai, Shanci Wang, Guixing Cai, Dingheng Lu, Zhen Sun, Qiang Wei
The role of leukemia inhibitory factor receptor (LIFR), which is important in the signal transduction of the interleukin-6 cytokine family, is still undefined in clear cell renal cell carcinoma (ccRCC). Thus, we examined the function and mechanism of LIFR in ccRCC. Low LIFR expression correlated with a poor prognosis and an aggressive tumor phenotype. Moreover, integrated LIFR DNA and mRNA analysis revealed that promoter methylation and copy number variation contributed to the reduced LIFR expression. LIFR knockdown increased 786-O and Caki-2 cell invasion and migration...
June 14, 2018: DNA and Cell Biology
Christopher R Rowland, Katherine A Glass, Adarsh R Ettyreddy, Catherine C Gloss, Jared R L Matthews, Nguyen P T Huynh, Farshid Guilak
Cartilage-derived matrix (CDM) has emerged as a promising scaffold material for tissue engineering of cartilage and bone due to its native chondroinductive capacity and its ability to support endochondral ossification. Because it consists of native tissue, CDM can undergo cellular remodeling, which can promote integration with host tissue and enables it to be degraded and replaced by neotissue over time. However, enzymatic degradation of decellularized tissues can occur unpredictably and may not allow sufficient time for mechanically competent tissue to form, especially in the harsh inflammatory environment of a diseased joint...
May 30, 2018: Biomaterials
Yanglei Yi, Fan Zhao, Nan Wang, Huan Liu, Lijun Yu, Aihua Wang, Yaping Jin
T-2 toxin is one of the trichothecene mycotoxins commonly found in animal feed and agricultural products. Ingestion of T-2 toxin by animals results in acute and chronic diseases, as well as reproductive failure. This study aimed at investigating the role of endoplasmic reticulum (ER) stress in T-2 toxin-induced apoptosis in goat endometrium epithelial cells. Flow cytometry and cell viability assay showed that T-2 toxin significantly induced cell apoptosis, which was accompanied with increased expression of cleaved-caspase-3...
June 12, 2018: Journal of Applied Toxicology: JAT
Qian Li, Guangying Chen, Hui Chen, Weijie Zhang, Yangyang Ding, Ping Yu, Ting Zhao, Guanghua Mao, Weiwei Feng, Liuqing Yang, Xiangyang Wu
To assess the immunomodulatory and antioxidant activities of a Se-polysaccharide from Se-enriched G. frondosa (Se-GFP-22), immunosuppressed mice models were generated by cyclophosphamide (CTX) administration and then treated with Se-GFP-22. Results showed that Se-GFP-22 could increase thymus and spleen indices, phagocytic index, co-mitogenic (ConA- or LPS-stimulated) activities on splenocytes, DTH reaction, serum hemolysin formation and immunoglobulin (Ig G, Ig A and Ig M) levels in CTX-treated mice. Se-GFP-22 significantly enhanced the antioxidant activity in CTX-treated mice, as shown by the evaluation of GSH-Px, SOD and CAT activities, as well as MDA levels in serum, liver and kidney...
September 15, 2018: Carbohydrate Polymers
Lin Li, Debo Yun, Yuan Zhang, Yihao Tao, Qiang Tan, Fei Qiao, Bo Luo, Yi Liu, Runjin Fan, Jishu Xian, Anyong Yu
BACKGROUND AND PURPOSE: The blood-brain barrier (BBB) disruption and the following development of brain edema, is the most life-threatening secondary injury after intracerebral hemorrhage (ICH). This study is to investigate a potential role and mechanism of JWH133, a selected cannabinoid receptor type2 (CB2R) agonist, on protecting blood-brain barrier integrity after ICH. METHODS: 192 adult male Sprague-Dawley (SD) rats were randomly divided into Sham; ICH+Vehicle; ICH+JWH 1...
June 7, 2018: Brain Research
Jiayan Wu, Guangbin Liu, Yongcan Sun, Xuepeng Wang, Hao Fang, Heng Jiang, Zhiming Guo, Jinggang Dong
The animal intestine provides a competitive environment for the microbiota. Successful colonization by pathogens requires sensing chemical signals to regulate the expression of virulence genes. Some bacteria rely on a two-component chemical signal transduction system, named FusKR, to regulate virulence genes expression by intestinal fucose. Here we construct the fucP gene deletion strain prove FucP regulation of the T3SS in E. tarda. The result showed that the mutant strain had down-regulated significantly the gene expression of FusKR and T3SS compared to the wild-type strain (p < 0...
June 7, 2018: Fish & Shellfish Immunology
Ting-Ting Zhang, Rui Xue, Shi-Yong Fan, Qiong-Yin Fan, Lei An, Juan Li, Lei Zhu, Yu-Hua Ran, Li-Ming Zhang, Bo-Hua Zhong, Yun-Feng Li, Cai-Ying Ye, You-Zhi Zhang
BACKGROUND: Diabetic neuropathic pain (DNP) is a common and distressing complication in patients with diabetes, and the underlying mechanism remains unclear. Tricyclic antidepressants (TCAs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) are recommended as first-line drugs for DNP. Ammoxetine is a novel and potent SNRI that exhibited a strong analgesic effect on models of neuropathic pain, fibromyalgia-related pain, and inflammatory pain in our primary study. The present study was undertaken to investigate the chronic treatment properties of ammoxetine on DNP and the underlying mechanisms for its effects...
June 7, 2018: Journal of Neuroinflammation
Katsunori Yoshida, Koichi Matsuzaki, Miki Murata, Takashi Yamaguchi, Kanehiko Suwa, Kazuichi Okazaki
Chronic viral hepatitis is a global public health problem, with approximately 570 million persons chronically infected. Hepatitis B and C viruses increase the risk of morbidity and mortality from liver cirrhosis, hepatocellular carcinoma (HCC), and extrahepatic complications that develop. Hepatitis virus infection induces transforming growth factor (TGF)-β, which influences microenvironments within the infected liver. TGF-β promotes liver fibrosis by up-regulating extracellular matrix production by hepatic stellate cells...
June 5, 2018: Cancers
Anh Duc Truong, Yeojin Hong, Janggeun Lee, Kyungbaek Lee, Dong Yong Kil, Hyun S Lillehoj, Yeong Ho Hong
Interleukin-34 (IL-34) is a newly recognized cytokine with functions similar to macrophage colony-stimulating factor 1. It is expressed in macrophages and fibroblasts, where it induces cytokine production; however, the mechanism of chicken IL-34 (chIL-34) signaling has not been identified to date. The aim of this study was to analyze the signal transduction pathways and specific biological functions associated with chIL-34 in chicken macrophage (HD11) and fibroblast (OU2) cell lines. We found that IL-34 is a functional ligand for the colony-stimulating factor receptor (CSF-1R) in chicken cell lines...
June 5, 2018: International Journal of Molecular Sciences
Vanessa Martins, Walcy Rosolia Teodoro, Ana Paula Pereira Velosa, Priscila Andrade, Cecília Farhat, Alexandre Todorovic Fabro, Vera Luiza Capelozzi
Anomalous histoarchitecture with increased levels of type-V collagen (Col V) in lungs of human idiopathic pulmonary fibrosis (IPF) and bleomycin (BLM) airway-centered interstitial fibrosis suggest that this collagen can be a possible trigger involved in the pathogenesis of these diseases. Butylated hydroxytoluene (BHT) injury model revealed a distal involvement of lung parenchyma with significant endothelial injury and fibrotic response, contrasting with the BLM airway-centered insult. We undertook this study to analyze whether BHT alters distal airway/alveolar epithelial cells (AECs) and extracellular matrix (ECM) signaling involved in the initiation and progression of pulmonary fibrosis in a different pathway concerning overexpression of Col V...
June 5, 2018: Histology and Histopathology
Mahssa Hassan-Nejhad, Morteza Bagheri, Kamal Khadem-Vatani, Mir Hossein Seyed Mohammad Zad, Isa Abdi Rad, Behzad Rahimi, Ali Rostamzadeh, Amir Rahimlou
Background: Coronary artery disease is the leading cause of disability and mortality in Iran and worldwide. Tumor necrosis factor-alpha is a pro-inflammatory cytokine that plays a key role in inflammatory cascades and atherosclerosis. It regulates cytokine networks and adhesion molecule expression, and activates several signal transduction pathways, being also known as transducer of cardiovascular diseases, especially premature coronary artery disease. Objective: The aim of the present study was to investigate tumor necrosis factor-alpha gene expression in Iranian Azeri Turkish patients with premature coronary artery disease (age ≤50 years)...
March 2018: Mædica
Youn Kyung Choi, Bo-Ram Ye, Eun-A Kim, Junseong Kim, Min-Sun Kim, Won Woo Lee, Gin-Nae Ahn, Nalae Kang, Won-Kyo Jung, Soo-Jin Heo
Inflammation is a pathophysiological defense response against various factors for maintaining homeostasis in the body. However, when continued excessive inflammation becomes chronic, various chronic diseases can develop. Therefore, effective treatment before chronic inflammation development is essential. Bis (3-bromo-4,5-dihydroxybenzyl) ether (BBDE, C14 H12 Br2 O5 ) is a novel bromophenol isolated from the red alga Polysiphonia morrowii. The beneficial physiological functions of various bromophenols are known, but whether BBDE has beneficial physiological functions is unknown...
July 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Fengxiang Wei, Peng Hao, Xiangzhong Zhang, Haiyan Hu, Dan Jiang, Aihua Yin, Lijuan Wen, Lihong Zheng, Jeffrey Zheru He, Wenjuan Mei, Hui Zeng, Damu Tang
DNA damage response (DDR) coordinates lesion repair and checkpoint activation. DDR is intimately connected with transcription. However, the relationship between DDR and transcription has not been clearly established. We report here RNA-sequencing analyses of MCF7 cells containing double-strand breaks induced by etoposide. While etoposide does not apparently cause global changes in mRNA abundance, it altered some gene expression. At the setting of fold alteration ≥ 2 and false discovery rate (FDR) ≤ 0.001, FDR < 0...
May 8, 2018: Oncotarget
Dietrich A Ruess, Guus J Heynen, Katrin J Ciecielski, Jiaoyu Ai, Alexandra Berninger, Derya Kabacaoglu, Kivanc Görgülü, Zahra Dantes, Sonja M Wörmann, Kalliope N Diakopoulos, Angeliki F Karpathaki, Marlena Kowalska, Ezgi Kaya-Aksoy, Liang Song, Eveline A Zeeuw van der Laan, María P López-Alberca, Marc Nazaré, Maximilian Reichert, Dieter Saur, Mert M Erkan, Ulrich T Hopt, Bruno Sainz, Walter Birchmeier, Roland M Schmid, Marina Lesina, Hana Algül
The ubiquitously expressed non-receptor protein tyrosine phosphatase SHP2, encoded by PTPN11, is involved in signal transduction downstream of multiple growth factor, cytokine and integrin receptors 1 . Its requirement for complete RAS-MAPK activation and its role as a negative regulator of JAK-STAT signaling have established SHP2 as an essential player in oncogenic signaling pathways1-7 . Recently, a novel potent allosteric SHP2 inhibitor was presented as a viable therapeutic option for receptor tyrosine kinase-driven cancers, but was shown to be ineffective in KRAS-mutant tumor cell lines in vitro 8 ...
May 28, 2018: Nature Medicine
Erika Engelowski, Artur Schneider, Manuel Franke, Haifeng Xu, Ramona Clemen, Alexander Lang, Paul Baran, Christian Binsch, Birgit Knebel, Hadi Al-Hasani, Jens M Moll, Doreen M Floß, Philipp A Lang, Jürgen Scheller
Cytokine-induced signal transduction is executed by natural biological switches, which among many others control immune-related processes. Here, we show that synthetic cytokine receptors (SyCyRs) can induce cytokine signaling using non-physiological ligands. High-affinity GFP- and mCherry-nanobodies were fused to transmembrane and intracellular domains of the IL-6/IL-11 and IL-23 cytokine receptors gp130 and IL-12Rβ1/IL-23R, respectively. Homo- and heterodimeric GFP:mCherry fusion proteins as synthetic cytokine-like ligands were able to induce canonical signaling in vitro and in vivo...
May 23, 2018: Nature Communications
Jingqi Ren, Yaqiu Lin, Junni Tang, Hua Yue, Yanying Zhao
BACKGROUND/AIMS: Allograft inflammatory factor-1 (AIF-1) is an inflammatory cytokine produced mainly by macrophages within human white adipose tissue. Its expression is increased in obese subjects and positively correlated with insulin resistance. The purpose of this study is to characterize the regulatory role of AIF-1 in insulin signaling of adipocyte. METHODS: AIF-1 was over-expressed via transfection of AIF-1 cDNA into murine RAW 264.7 macrophages, and the constitutive expression of AIF-1 was decreased via transfection of targeting siRNA...
May 18, 2018: Cellular Physiology and Biochemistry
Jialei Zhu, Zhaoli Hu, Xiaojuan Han, Dongshuo Wang, Qingling Jiang, Jianhua Ding, Ming Xiao, Cong Wang, Ming Lu, Gang Hu
Astrocytes are involved in the neuroinflammation of neurodegenerative diseases, such as Parkinson's disease (PD). Among the numerous inflammatory cytokines, interleukin-1β (IL-1β) produced by astrocytic Nod-like receptor protein (NLRP) inflammasome is crucial in the pathogenesis of PD. β-arrestin2-mediated dopamine D2 receptor (Drd2) signal transduction has been regarded as a potential anti-inflammatory target. Our previous study revealed that astrocytic Drd2 suppresses neuroinflammation in the central nervous system...
May 21, 2018: Cell Death and Differentiation
Weiwei Sun, Rongqin Qin, Rui Wang, Dazhi Ding, Zhaohui Yu, Yuxi Liu, Ruilong Hong, Zhen Cheng, Youhua Wang
Src-associated substrate during mitosis of 68 KDa (Sam68), also known as KH domain containing, RNA binding, signal transduction associated 1 (KHDRBS1), is the prototypic member of the signal transduction activator of RNA (STAR) family of RNA-binding proteins. Previous studies have indicated that Sam68 regulates nuclear transcription factor kappa B (NF-κB) to mediate inflammation. In this study, we analyzed the effect and possible mechanisms of Sam68 in rheumatoid arthritis (RA). By western blot analysis and immunohistochemistry, we found that the expression of Sam68 in synovial tissue of RA patients was increased compared with the control group...
May 21, 2018: Inflammation
Haiyan Yan, Huiqiang Wang, Linlin Ma, Xueping Ma, Jinqiu Yin, Shuo Wu, Hua Huang, Yuhuan Li
BACKGROUND: Artemisia scoparia Waldst and Kit is a famous traditional Chinese medicine widely distributed in Xinjiang, China. Flavonoids extracted from it exhibits inhibitory activities against several influenza virus strains. Despite this fact, the antiviral properties of CST, one of such flavonoids, against the influenza virus has not been reported. Thus, the aim of this study is to investigate the anti-influenza virus efficacy and antiviral mechanism of CST. METHODS: The inhibitory activity of CST against influenza viruses was assessed by using viral titers and performing Western blot, qRT-PCR, and immunofluorescence assays in Madin-Darby canine kidney (MDCK) cells and a human monocytic cell line (THP-1)...
May 21, 2018: Virology Journal
Pradip Bajgain, Supannikar Tawinwung, Lindsey D'Elia, Sujita Sukumaran, Norihiro Watanabe, Valentina Hoyos, Premal Lulla, Malcolm K Brenner, Ann M Leen, Juan F Vera
BACKGROUND: The adoptive transfer of T cells redirected to tumor via chimeric antigen receptors (CARs) has produced clinical benefits for the treatment of hematologic diseases. To extend this approach to breast cancer, we generated CAR T cells directed against mucin1 (MUC1), an aberrantly glycosylated neoantigen that is overexpressed by malignant cells and whose expression has been correlated with poor prognosis. Furthermore, to protect our tumor-targeted cells from the elevated levels of immune-inhibitory cytokines present in the tumor milieu, we co-expressed an inverted cytokine receptor linking the IL4 receptor exodomain with the IL7 receptor endodomain (4/7ICR) in order to transform the suppressive IL4 signal into one that would enhance the anti-tumor effects of our CAR T cells at the tumor site...
May 10, 2018: Journal for Immunotherapy of Cancer
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