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Cinthia C Stempin, Claudia C Motrán, María P Aoki, Cristian R Falcón, Fabio M Cerbán, Laura Cervi
Macrophage plasticity is critical for controlling inflammation including those produced by helminth infections, where alternatively activated macrophages (AAM) are accumulated in tissues. AAM expressing the co-inhibitory molecule programmed death ligand 2 (PD-L2), which is capable of binding programmed death 1 (PD-1) expressed on activated T cells, have been demonstrated in different parasitic infections. However, the role of PD-L2 during F. hepatica infection has not yet been explored. We observed that F. hepatica infection or a F...
October 21, 2016: Oncotarget
Patrick T Walsh, Padraic G Fallon
The recently discovered interleukin (IL)-36 family of cytokines form part of the broader IL-1 family and are emerging as important mediators of inflammatory disease. The IL-36 subfamily consists of three ligands-IL-36α, IL-36β, and IL-36γ-and the natural antagonist IL-36Ra. The cytokines exert their effects through a specific IL-36 receptor consisting of IL-36R and IL-1RAcP chains. IL-36 cytokines can direct both innate and adaptive immune responses by acting on parenchymal, stromal, and specific immune cell subsets...
October 26, 2016: Annals of the New York Academy of Sciences
Carlos Fernandez-Patron, Zamaneh Kassiri, Dickson Leung
Matrix metalloproteinase-2 (MMP-2) is a 72-kDa zinc- and calcium-dependent endopeptidase with intracellular and extracellular functions ranging from the modulation of extracellular matrix remodeling to cell growth and migration, angiogenesis, inflammation, and metabolism. An upregulation of MMP-2 activity has the potential to deregulate lipid metabolism through the cleavage of numerous metabolic mediators including plasma lipoproteins and cell surface receptors of lipoproteins. Paradoxically, MMP-2 deficiency induces inflammation and deregulates metabolism...
September 15, 2016: Comprehensive Physiology
Hiroshi Kaji
Adipose tissue has recently been reevaluated as an endocrine organ, and adipose-tissue-derived endocrine factors are termed adipokines. Plasminogen activator inhibitor-1 (PAI-1) is the primary inhibitor of PAs, which convert plasminogen into plasmin, a critical protease involved in fibrinolysis. PAI-1 induces fibrinogenesis by suppressing intravascular and tissue fibrinolysis. Moreover, PAI-1 exerts various cellular effects independently of fibrinolysis. Although PAI-1 is expressed in various tissues, its expression is regulated by numerous growth factors, cytokines, and hormones in a paracrine and endocrine manner...
September 15, 2016: Comprehensive Physiology
Laura Denise Mendes da Silva, Mariana Gatto, Mariana Miziara de Abreu Teodoro, Marjorie de Assis Golim, Érika Alessandra Pelisson Nunes da Costa, Francilene Capel Tavares Carvalho, Daniela Ramos Rodrigues, Paulo Câmara Marques Pereira, Ângela Maria Victoriano de Campos Soares, Sueli Aparecida Calvi
Chagas disease (CD), caused by the protozoan Trypanosoma cruzi is a serious public health issue. Its evolution involves an acute stage, characterized by no specific symptoms, and the chronic stage during most individuals are asymptomatic, but about 30 to 40% of them become symptomatic presenting the cardiac or digestive disease. Host immune response mechanisms involved in symptomatic or asymptomatic chronic disease are not fully understood. The pro-inflammatory cytokines are crucial in host resistance. However, a fine control of this inflammatory process, by action of anti-inflammatory cytokines, is necessary to avoid tissue injury...
October 26, 2016: Scandinavian Journal of Immunology
C D C Neves, A C R Lacerda, V K S Lage, L P Lima, R Tossige-Gomes, S F Fonseca, E Rocha-Vieira, M M Teixeira, V A Mendonça
Chronic exposure to cigarette smoke seems to be related to an increase of pro-inflammatory cytokines, oxidative stress and changes in muscular and physical performances of healthy smokers. However, these parameters have not yet been evaluated simultaneously in previous studies. The participants of this study were healthy males divided into two groups: smokers (n=20) and non-smokers (n=20). Inflammation was evaluated by measuring plasma levels of the cytokines IL-10, IL-6 e TNF-α, and of the soluble receptors sTNFR1 and sTNFR2...
October 24, 2016: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
Sérgio Ferreira de Lima, Mayara Mansur Fernandes Tavares, Jamilly Lopes de Macedo, Renata Santos de Oliveira, Sandra de Andrade Heráclio, Maria de Mascena Diniz Maia, Paulo Roberto Eleutério de Souza, Ronald Moura, Sergio Crovella
Human papillomavirus (HPV) infections are strongly associated with the development of cervical intraepithelial neoplasias and invasive cervical cancer. Polymorphisms in cytokine-encoding genes and behavioural cofactors could play an important role in protecting an individual against viral infections and cancer. Here, we investigated whether IL-6 -174 G>C, IL-8 +396 G>T, and TGF-β1 +869 G>C and +915 G>C polymorphisms were associated with susceptibility to HPV infection in women from north-east (Pernambuco) Brazil...
October 24, 2016: Memórias do Instituto Oswaldo Cruz
Rahul Agrawal, Tina P Dale, Mohammed A Al-Zubaidi, Prit Benny Malgulwar, Nicholas R Forsyth, Ritu Kulshreshtha
MicroRNAs are reported to have a crucial role in the regulation of self-renewal and differentiation of stem cells. Hypoxia has been identified as a key biophysical element of the stem cell culture milieu however, the link between hypoxia and miRNA expression in stem cells remains poorly understood. We therefore explored miRNA expression in hypoxic human embryonic and mesenchymal stem cells (hESCs and hMSCs). A total of 50 and 76 miRNAs were differentially regulated by hypoxia (2% O2) in hESCs and hMSCs, respectively, with a negligible overlap of only three miRNAs...
2016: PloS One
Kshipra Singh, Nicole T Al-Greene, Thomas G Verriere, Lori A Coburn, Mohammad Asim, Daniel P Barry, Margaret M Allaman, Dana M Hardbower, Alberto G Delgado, M Blanca Piazuelo, Bruce A Vallance, Alain P Gobert, Keith T Wilson
Solute carrier family 7 member 2 (SLC7A2) is an inducible transporter of the semi-essential amino acid L-arginine (L-Arg), which has been implicated in immune responses to pathogens. We assessed the role of SLC7A2 in murine infection with Citrobacter rodentium, an attaching and effacing enteric pathogen that causes colitis. Induction of SLC7A2 was upregulated in colitis tissues, and localized predominantly to colonic epithelial cells. Compared to wild-type mice, Slc7a2-/-mice infected with C. rodentium had improved survival and decreased weight loss, colon weight, and histologic injury; this was associated with decreased colonic macrophages, dendritic cells, granulocytes, and Th1 and Th17 cells...
October 2016: PLoS Pathogens
Satyanarayana Swamy Cheekatla, Deepak Tripathi, Sambasivan Venkatasubramanian, Pavan Kumar Nathella, Padmaja Paidipally, Munenori Ishibashi, Elwyn Welch, Amy R Tvinnereim, Mitsuo Ikebe, Vijaya Lakshmi Valluri, Subash Babu, Hardy Kornfeld, Ramakrishna Vankayalapati
In this study, we developed a mouse model of type 2 diabetes mellitus (T2DM) using streptozotocin and nicotinamide and identified factors that increase susceptibility of T2DM mice to infection by Mycobacterium tuberculosis (Mtb). All Mtb-infected T2DM mice and 40% of uninfected T2DM mice died within 10 months, whereas all control mice survived. In Mtb-infected mice, T2DM increased the bacterial burden and pro- and anti-inflammatory cytokine and chemokine production in the lungs relative to those in uninfected T2DM mice and infected control mice...
October 2016: PLoS Pathogens
Alexandra Sufit, Alisa B Lee-Sherick, Deborah DeRyckere, Manali Rupji, Bhakti Dwivedi, Marileila Varella-Garcia, Angela M Pierce, Jeanne Kowalski, Xiaodong Wang, Stephen V Frye, H Shelton Earp, Amy K Keating, Douglas K Graham
BACKGROUND: MER receptor tyrosine kinase (MERTK) is expressed in a variety of malignancies, including glioblastoma multiforme (GBM). Our previous work demonstrated that inhibition of MERTK using RNA interference induced cell death and chemosensitivity in GBM cells, implicating MERTK as a potential therapeutic target. Here we investigate whether a novel MERTK-selective small molecule tyrosine kinase inhibitor, UNC2025, has similar anti-tumor effects in GBM cell lines. METHODS: Correlations between expression of GAS6, a MERTK ligand, and prognosis were determined using data from the TCGA database...
2016: PloS One
Ines Rama, Ines Llaudó, Pere Fontova, Gema Cerezo, Carlos Soto, Casimiro Javierre, Miguel Hueso, Nuria Montero, Alberto Martínez-Castelao, Juan Torras, Josep M Grinyó, Josep M Cruzado, Nuria Lloberas
BACKGROUND: Patients undergoing conventional hemodialysis (C-HD) present a greater immuno-inflammatory state probably related to uremia, sympathetic nervous system (SNS) activation and /or membrane bioincompatibility, which could improve with a technique-switching to online hemodiafiltration (OL-HD). The antigen-independent pathway activation of this modified immunologic state turns dendritic cells (DC) into an accurate cell model to study these patients. The aim of this study is to further evaluate the immune-inflammatory state of patients in C-HD assessed by DC maturation...
2016: PloS One
Lei Dong, Wen-Mei Yu, Hong Zheng, Mignon L Loh, Silvia T Bunting, Melinda Pauly, Gang Huang, Muxiang Zhou, Hal E Broxmeyer, David T Scadden, Cheng-Kui Qu
Germline activating mutations of the protein tyrosine phosphatase SHP2 (encoded by PTPN11), a positive regulator of the RAS signalling pathway, are found in 50% of patients with Noonan syndrome. These patients have an increased risk of developing leukaemia, especially juvenile myelomonocytic leukaemia (JMML), a childhood myeloproliferative neoplasm (MPN). Previous studies have demonstrated that mutations in Ptpn11 induce a JMML-like MPN through cell-autonomous mechanisms that are dependent on Shp2 catalytic activity...
October 26, 2016: Nature
Thierry Lioux, Marc-Antoine Mauny, Alain Lamoureux, Nicolas Bascoul, Mathieu Hays, Fabienne Vernejoul, Anne-Sophie Baudru, Cédric Boularan, Justine Lopes-Vicente, Gregory Qushair, Gérard Tiraby
We describe novel STING-activating cyclic dinucleotides whose constituent nucleosides are adenosine and inosine, and that vary by ribose substitution, internucleotide linkage position and phosphate modification. In mammalian cells in vitro, some of these cAIMP analogs induce greater STING-dependent IRF and NF-κB pathway signaling than do the reference agonists for murine (DMXAA) or human (2',3'-cGAMP) STING. In human blood ex vivo, they induce type I interferons (IFNs) and pro-inflammatory cytokines: for the former, 3',3'-cAIMP (9; EC50: 6...
October 26, 2016: Journal of Medicinal Chemistry
Qing Liu, Dinghong Wu, Ling Han, Jingwen Deng, Li Zhou, Rui He, Chuanjian Lu, Qing-Sheng Mi
MicroRNAs (miRNAs) are small non-coding RNA molecules, which function in RNA silencing and post-transcriptional regulation of gene expression. Psoriasis is an inflammatory skin disease characterized by the dysfunction of keratinocytes, with the immune dysregulation. We reviewed the recent studies on the roles of miRNAs in psoriasis, and showed that miRNAs play key roles in psoriasis, including the regulation of hyperproliferation, cytokine and chemokine production in keratinocyte, as well as mediating immune dysfunction in psoriasis...
October 26, 2016: Experimental Dermatology
Muna Sapkota, Kusum K Kharbanda, Todd A Wyatt
BACKGROUND: Reactive aldehydes such as acetaldehyde and malondialdehyde generated as a result of alcohol metabolism and cigarette smoke exposure lead to the formation of malondialdehyde-acetaldehyde-adducted proteins (MAA adducts). These aldehydes can adduct to different proteins such as bovine serum albumin and surfactant protein A or surfactant protein D (SPD). Macrophages play an important role in innate immunity, but the effect of MAA adducts on macrophage function has not yet been examined...
October 26, 2016: Alcoholism, Clinical and Experimental Research
T A Danilova, G A Danilina, A A Adzhieva, A G Minko, V G Zhukhovitskii
Dynamics of IL-6 level was studied in blood serum of CBA mice receiving intraperitoneal injections of killed and live culture of group A Streptococcus and its supernatants. It was found that administration of killed culture was followed by a significant rise in IL-6 level (by 4.7 times in 1 h and by 9.3 times in 5 h in comparison with the control). By 24 h, cytokine content was below the control. The highest levels of IL-6 were found after treatment with supernatants of Streptococcus cultures (by 10.5 times in 1 h and by 14...
October 26, 2016: Bulletin of Experimental Biology and Medicine
D L Misner, M A Kauss, J Singh, H Uppal, A Bruening-Wright, B M Liederer, T Lin, B McCray, N La, T Nguyen, D Sampath, P S Dragovich, T O'Brien, T S Zabka
Nicotinamide phosphoribosyltransferase (NAMPT) is a pleiotropic protein that functions as an enzyme, cytokine, growth factor and hormone. As a target for oncology, NAMPT is particularly attractive, because it catalyzes the rate-limiting step in the salvage pathway to generate nicotinamide adenine dinucleotide (NAD), a universal energy- and signal-carrying molecule involved in cellular energy metabolism and many homeostatic functions. Inhibition of NAMPT generally results in NAD depletion, followed by ATP reduction and loss of cell viability...
October 25, 2016: Cardiovascular Toxicology
Sarah Kado, W L William Chang, Aimy Nguyen Chi, Monika Wolny, David M Shepherd, Christoph F A Vogel
Currently, it is not well understood how ligands of the aryl hydrocarbon receptor (AhR) modify inflammatory responses triggered by Toll-like receptor (TLR) agonists in human dendritic cells (DCs). Here, we show that AhR ligands 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the tryptophan derivatives 6-formylindolo[3,2-b] carbazole (FICZ), kynurenine (kyn), and the natural dietary compound indole-3-carbinol (I3C) differentially modify cytokine expression in human monocyte-derived DCs (MoDCs). The results show that TLR-activated MoDCs express higher levels of AhR and are more sensitive toward the effects of AhR ligands...
October 25, 2016: Archives of Toxicology
Yang Chen, Lei Wang, Ashley L Pitzer, Xiang Li, Pin-Lan Li, Yang Zhang
: Recent studies indicate that inflammasomes serve as intracellular machinery to initiate classical cytokine-mediated inflammatory responses and play a crucial role in the pathogenesis of cardiovascular diseases. However, whether or not the activation of endothelial inflammasomes directly causes cell dysfunction or tissue injury without recruitment of inflammatory cells is unknown. We explored the role of endothelial cell inflammasome activation in mediating tight junction disruption, a hallmark event of endothelial barrier dysfunction leading to endothelial hyperpermeability in diabetes...
October 25, 2016: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
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