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Mediators of Inflammation

Pazit Y Cohen, Raphael Breuer, Shulamit B Wallach-Dayan
Lung fibrosis is characterized by abnormal accumulation of Thy-deficient fibroblasts in the interstitium of the alveolar space. We have previously shown in bleomycin-treated chimeric Thy1-deficient mice with wild-type lymphocytes that Thy1-deficient fibroblasts accumulate and promote fibrosis and an "inflammation-free" environment. Here, we aimed to identify the critical effects of Thy1, or the absence of Thy1, in lung myofibroblast profibrotic functions, particularly proliferation and collagen deposition...
2018: Mediators of Inflammation
David A C Messerer, Stephanie Denk, Karl J Föhr, Rebecca Halbgebauer, Christian K Braun, Felix Hönes, Julia Harant, Michael Fauler, Manfred Frick, Benedikt L Nußbaum, Peter Radermacher, Sebastian Hafner, Markus S Huber-Lang
Background: Polymorphonuclear granulocytes (PMN) play a crucial role in host defense. Physiologically, exposure of PMN to the complement activation product C5a results in a protective response against pathogens, whereas in the case of systemic inflammation, excessive C5a substantially impairs neutrophil functions. To further elucidate the inability of PMN to properly respond to C5a, this study investigates the role of the cellular membrane potential of PMN in response to C5a. Methods: Electrophysiological changes in cellular and mitochondrial membrane potential and intracellular pH of PMN from human healthy volunteers were determined by flow cytometry after exposure to C5a...
2018: Mediators of Inflammation
Carolina Cubillos-Zapata, Enrique Hernández-Jiménez, José Avendaño-Ortiz, Victor Toledano, Anibal Varela-Serrano, Isabel Fernández-Navarro, Raquel Casitas, Carlos Carpio, Luis A Aguirre, Francisco García-Río, Eduardo López-Collazo
Obstructive sleep apnea (OSA) is a syndrome characterized by repeated pauses in breathing induced by a partial or complete collapse of the upper airways during sleep. Intermittent hypoxia (IH), a hallmark characteristic of OSA, has been proposed to be a major determinant of cancer development, and patients with OSA are at a higher risk of tumors. Both OSA and healthy monocytes have been found to show enhanced HIF1 α expression under IH. Moreover, these cells under IH polarize toward a tumor-promoting phenotype in a HIF1 α -dependent manner and influence tumor growth via vascular endothelial growth factor (VEGF)...
2018: Mediators of Inflammation
Megan Lynn, Laura Maclachlan, Andreas Finkelmeyer, James Clark, James Locke, Stephen Todryk, Wan-Fai Ng, Julia L Newton, Stuart Watson
Glucocorticoid receptor (GR) function may have aetiopathogenic significance in chronic fatigue syndrome (CFS), via its essential role in mediating inflammatory responses as well as in hypothalamic-pituitary-adrenal axis regulation. GR function can be estimated ex vivo by measuring dexamethasone (dex) modulation of cytokine response to lipopolysaccharide (LPS), and in vivo using the impact of dex on cortisol levels. This study aimed to compare the GR function between CFS ( n = 48), primary Sjögren's syndrome (a disease group control) ( n = 27), and sedentary healthy controls (HCs) ( n = 20), and to investigate its relationship with clinical measures...
2018: Mediators of Inflammation
Yisong Qian, Chuqiao Chen, Leliang Ma, Ziwei Wang, Ling-Fang Wang, Li Zuo, Yaqin Yang, Xiang Huang, Meixiu Jiang, Xiaolei Wang, Huidong Shi, Mingui Fu, Ke-Yu Deng, Hong-Bo Xin
CD38 was first identified as a lymphocyte-specific antigen and then has been found to be widely expressed in a variety of cell types. The functions of CD38 are involved in numerous biological processes including immune responses. Here, we showed the downregulations of both TLR2 mRNA and protein in macrophages from CD38-/- mice and in CD38 knockdown RAW264.7 cells. Several NF- κ B-binding motifs in the promoter region of the TLR2 gene were identified by the bioinformatics analysis and were confirmed by the luciferase activity assay with the different truncated TLR2 promoters...
2018: Mediators of Inflammation
Geórgia Nascimento Saraiva, Natalia Fonseca do Rosário, Thalia Medeiros, Paulo Emílio Côrrea Leite, Gilmar de Souza Lacerda, Thaís Guaraná de Andrade, Elzinandes Leal de Azeredo, Petronela Ancuta, Jorge Reis Almeida, Analúcia Rampazzo Xavier, Andrea Alice Silva
This study aimed at analyzing circulating levels of inflammatory and profibrogenic cytokines in patients with hepatitis C virus (HCV) chronic infection undergoing therapy with direct-acting antiviral agents (DAA) and correlating these immune biomarkers with liver disease status. We studied 88 Brazilian monoinfected chronic hepatitis C patients receiving interferon- (IFN-) free sofosbuvir-based regimens for 12 or 24 weeks, followed-up before therapy initiation and three months after the end of treatment. Liver disease was determined by transient elastography, in addition to APRI and FIB-4 indexes...
2018: Mediators of Inflammation
Smita Shukla, Carly Levine, Roopa Payanur Sripathi, Genie Elson, Carol Susan Lutz, Samuel Joseph Leibovich
Epigenetic modulators, including histone methylases, demethylases, and deacetylases, have been implicated previously in the regulation of classical and alternative macrophage activation pathways. In this study, we show that the histone acetyl transferase (HAT) Kat6B (MYST4) is strongly suppressed (>80%) in macrophages by lipopolysaccharide (LPS) (M1 activation), while Kat6A, its partner in the MOZ/MORF complex, is reciprocally upregulated. This pattern of expression is not altered by LPS together with the adenosine receptor agonist NECA (M2d activation)...
2018: Mediators of Inflammation
Fangui Min, Lifang He, Yinzhu Luo, Shuwu Huang, Jinchun Pan, Jing Wang, Ruike Wu, Lan Zhang, Meili Chen
To profile the dynamic changes of immune responses for M. kansasii infection, 3 cynomolgus monkeys were experimentally infected with M. kansasii by intratracheal inhalation of 1 × 106  CFU bacteria per monkey. Every 2 to 4 weeks, tuberculin skin testings (TSTs) were performed and blood samples were collected for immunoassay. Multiple cytokines in a single sample were measured by Luminex xMAP technologies. IgM and IgA were detected by double-antibody sandwich ELISA. IgG against PPD and 11 M. tuberculosis proteins were detected by using of indirect ELISA...
2018: Mediators of Inflammation
Yoonseo Kim, Nicole Noren Hooten, Michele K Evans
Growth differentiation factor 15 (GDF15) is a multifunctional, secreted protein that is a direct target gene of p53. GDF15 is a prospective biomarker of cardiovascular disease (CVD). C-reactive protein (CRP), like GDF15, is implicated in inflammation and an independent biomarker of CVD. However, the molecular interactions between GDF15 and CRP remain unexplored. In women, we found a significant relationship between hsCRP and GDF15 serum and mRNA levels. In vitro treatment of cultured human aortic endothelial cells (HAECs) with purified CRP or transfection of a CRP plasmid into HAECs induced GDF15 expression...
2018: Mediators of Inflammation
Chrissy H Roberts, Sander Ouburg, Mark D Preston, Henry J C de Vries, Martin J Holland, Servaas A Morré
Chlamydia trachomatis is the most commonly diagnosed bacterial sexually transmitted infection and can lead to tubal factor infertility, a disease characterised by fibrosis of the fallopian tubes. Genetic polymorphisms in molecular pathways involving G protein-coupled receptor signalling, the Akt/PI3K cascade, the mitotic cell cycle, and immune response have been identified in association with the development of trachomatous scarring, an ocular form of chlamydia-related fibrotic pathology. In this case-control study, we performed genome-wide association and pathways-based analysis in a sample of 71 Dutch women who attended an STI clinic who were seropositive for Chlamydia trachomatis antibodies and 169 high-risk Dutch women who sought similar health services but who were seronegative...
2018: Mediators of Inflammation
Francesca Colavita, Veronica Bordoni, Claudia Caglioti, Mirella Biava, Concetta Castilletti, Licia Bordi, Serena Quartu, Marco Iannetta, Giuseppe Ippolito, Chiara Agrati, Maria Rosaria Capobianchi, Eleonora Lalle
The recent epidemic in the Americas caused by Zika virus (ZIKV), Asian lineage, spurred the research towards a better understanding of how ZIKV infection affects the host immune response. The aim of this study was to evaluate the effects of Asian and East African ZIKV strain infection on the induction of IFN and proinflammatory and Th2 cytokines in human PBMC. We reported a slight modulation of type II IFN in PBMC exposed to Asian strain, but not to African strain, and a complete lack of type I and III IFN induction by both strains, suggesting the ability of ZIKV to evade the IFN system not only inhibiting the antiviral IFN response but also IFN production...
2018: Mediators of Inflammation
Monica Fengsrud Brinchmann, Deepti Manjari Patel, Martin Haugmo Iversen
Galectins are β -galcotosid-binding lectins. The function of galectins varies with their tissue-specific and subcellular location, and their binding to carbohydrates makes them key players in several intra- and extracellular processes where they bind to glycosylated proteins and lipids. In humans, there are 12 identified galectins, some with tissue-specific distribution. Galectins are found inside cells and in the nucleus, cytosol, and organelles, as well as extracellularly. Galectin-1, -2, -3, -4, -7, -8, -9, and -12 can all induce T-cell apoptosis and modulate inflammation...
2018: Mediators of Inflammation
Tao Zhu, Changyi Li, Xue Zhang, Chunyan Ye, Shuo Tang, Wei Zhang, Jiayang Sun, Niwen Huang, Fuqiang Wen, Daoxin Wang, Huojin Deng, Jing He, Di Qi, Wang Deng, Tao Yang
The reduction of pulmonary surfactant (PS) is essential for decreased pulmonary compliance and edema in acute lung injury (ALI). Thyroid transcription factor-1 (TTF-1) plays a major role in the regulation of surfactant protein-A (SP-A), the most abundant protein component of PS. Simultaneously, the glucagon-like peptide-1 (GLP-1) analogue can enhance SP-A expression in the lung. However, the underlying mechanism is still unknown. The purpose of this study was to explore whether liraglutide, a GLP-1 analogue, upregulates SP-A expression through the TTF-1 signaling pathway in ALI...
2018: Mediators of Inflammation
Jialian Zhao, Qiang Gu, Lifeng Wang, Weize Xu, Lihua Chu, Ya Wang, Zhongwang Li, Shuijing Wu, Jianguo Xu, Zhiyong Hu, Qiang Shu, Xiangming Fang
DEFA1/DEFA3, genes encoding human neutrophil peptides (HNP) 1-3, display wide-ranging copy number variations (CNVs) and is functionally associated with innate immunity and infections. To identify potential associations between DEFA1/DEFA3 CNV and hospital-acquired infections (HAIs), we enrolled 106 patients with HAIs and 109 controls in the intensive care unit (ICU) and examined their DEFA1/DEFA3 CNVs. DEFA1/DEFA3 copy number ranged from 2 to 16 per diploid genome in all 215 critically ill patients, with a median of 7 copies...
2018: Mediators of Inflammation
Xiaofang Huang, Huiqing Xiu, Shufang Zhang, Gensheng Zhang
Despite development in the understanding of the pathogenesis of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), the underlying mechanism still needs to be elucidated. Apart from leukocytes and endothelial cells, macrophages are also essential for the process of the inflammatory response in ALI/ARDS. Notably, macrophages play a dual role of proinflammation and anti-inflammation based on the microenvironment in different pathological stages. In the acute phase of ALI/ARDS, resident alveolar macrophages, typically expressing the alternatively activated phenotype (M2), shift into the classically activated phenotype (M1) and release various potent proinflammatory mediators...
2018: Mediators of Inflammation
Jing Yang, Man Qiao, Yanxia Li, Guohua Hu, Chunxia Song, Liping Xue, Hong Bai, Jie Yang, Xi Yang
Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is closely associated with airway inflammation including monocytes, lymphocytes, and neutrophils. Monocytes play an essential role in the pathogenesis of chronic obstructive pulmonary disease (COPD). To elucidate the association of circulating monocyte alteration with AECOPD, we analyzed monocyte subpopulation in the peripheral blood of 16 healthy volunteers and 22 AECOPD patients at the stages of admission and remission after clinical therapy...
2018: Mediators of Inflammation
Eun Jung Kyung, Hyun Bum Kim, Eun Sang Hwang, Seok Lee, Bup Kyung Choi, Jin Woong Kim, Hyung Joong Kim, Sang Moo Lim, Oh In Kwon, Eung Je Woo
In oriental medicine, curcumin is used to treat inflammatory diseases, and its anti-inflammatory effect has been reported in recent research. In this feasibility study, the hepatoprotective effect of curcumin was investigated using a rat liver cirrhosis model, which was induced with dimethylnitrosamine (DMN). Together with biochemical analysis, we used a magnetic resonance-based electrical conductivity imaging method to evaluate tissue conditions associated with a protective effect. The effects of curcumin treatment and lactulose treatment on liver cirrhosis were compared...
2018: Mediators of Inflammation
Wenming Hong, Pengying Zhang, Xinming Wang, Jiajie Tu, Wei Wei
MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression at the posttranscriptional level via direct binding to the 3'-untranslated region (UTR) of target mRNAs. Emerging evidence shows that miRNAs play crucial roles in controlling and modulating immune system-related diseases. This review focuses on the role played by miRNAs in fibroblast-like synoviocytes (FLS), which is a key cellular component within synovia, during the establishment and maintenance of rheumatoid arthritis (RA), a systemic inflammatory autoimmune disease...
2018: Mediators of Inflammation
Yun Hee Kim, Dong Eon Kim, Seung-Hyo Lee
Airway epithelial cells secrete diverse inflammatory mediators in response to various stimuli. Thus, early regulation of immune responses in the airway epithelium is likely critical for the control of chronic inflammatory diseases. The purpose of the present study was to evaluate the effects of 18 β -glycyrrhetinic acid (GA) on inflammatory responses generated in response to a fungal protease allergen that induces epithelial damage. To understand the underlying mechanisms, we also investigated the inhibitory effects of GA on the production of mitochondrial reactive oxygen species (ROS) in the human bronchial epithelial cell line BEAS2B...
2018: Mediators of Inflammation
Zhengyu Jiang, Yan Meng, Lulong Bo, Changli Wang, Jinjun Bian, Xiaoming Deng
Septic liver injury/failure that is mainly characterized by oxidative stress, inflammation, and apoptosis led to a great part of terminal liver pathology with limited effective intervention. Here, we used a lipopolysaccharide (LPS) stimulation model to simulate the septic liver injury and investigated the effect of sophocarpine on LPS-stimulated mice with endotoxemia. We found that sophocarpine increases the survival rate of mice and attenuates the LPS-induced liver injury, which is indicated by pathology and serum liver enzymes...
2018: Mediators of Inflammation
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