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Gabriela Maria Wiedemann, Max Martin Ludwig Knott, Viola Katharina Vetter, Moritz Rapp, Sascha Haubner, Julia Fesseler, Benjamin Kühnemuth, Patrick Layritz, Raffael Thaler, Stephan Kruger, Steffen Ormanns, Doris Mayr, Stefan Endres, David Anz
In cancer patients, immunosuppression through regulatory T cells (Treg) is a crucial component of tumor immune evasion and contributes to disease progression. Tumor-infiltrating Treg in particular suppress local effector T cell responses and are associated with poor prognosis in tumors such as human pancreatic cancer or hepatocellular carcinoma (HCC). The chemokine CCL22 is known to recruit Treg into the tumor tissue and many types of human tumors are known to express high levels of CCL22. The mechanisms leading to intratumoral secretion of CCL22 are so far unknown...
2016: Oncoimmunology
Paulina Płoszaj, Andrzej Regiec, Stanisław Ryng, Agnieszka Piwowar, Marian L Kruzel
The 5-amino-3-methyl-4-isoxazolecarboxylic acid hydrazide (HIX) is a synthetic isoxazole derivative with a potential for development as an anti-inflammatory drug candidate. The goal of this study was to explore in vitro autoimmune and inflammatory gene modulation by HIX in human Caco-2 cultured cells. The effect of low dose of HIX was tested on the expression level of RNA in 24h Caco-2 cultures using the QIAGEN Th17 for Autoimmunity & Inflammation RT(2) Profiler PCR Array. We choose the PCR technology as the most reliable and sensitive gene expression profiling method for analyzing specific gene regulatory networks...
October 17, 2016: Immunopharmacology and Immunotoxicology
Kristi J Warren, Xi Fang, Nagaraj M Gowda, Joshua J Thompson, Nicola M Heller
Lung M2 macrophages are regulators of airway inflammation, associated with poor lung function in allergic asthma. Previously, we demonstrated that IL-4-induced M2 gene expression correlated with tyrosine phosphorylation of the insulin receptor substrate (IRS)-2 in macrophages. We hypothesized that negative regulation of IRS-2 activity following IL-4 stimulation is dependent upon serine phosphorylation of IRS-2. Herein, we describe an inverse relationship between tyrosine phosphorylation (pY) and serine phosphorylation (pS) of IRS-2 following IL-4 stimulation...
October 14, 2016: Journal of Biological Chemistry
Chenggen Xiao, Qiaoling Zhou, Xiaozhao Li, Hui Li, Ting Meng, Yong Zhong, Jiaxi Pu, Mengyuan Zhu, Yan Xu, Lu Gan, Hong Sun, Ping Xiao
IL-22-producing helper T cells (Th22 cells) have been reported to be involved in lgA nephropathy. However, the mechanisms underlying the differentiation and immune regulation of Th22 cells in lgA nephropathy remain unknown. To elucidate the mechanisms by which Th22 cells differentiate and are recruited into the kidney in lgA nephropathy, the distribution of Th22 cells in both the kidney and blood was determined. Additionally, the impacts of proinflammatory cytokines and antigen presentation in the kidney on Th22 cell differentiation were explored...
2016: American Journal of Translational Research
Matthew N Davies, Helene Pere, Iris Bosschem, Freddy Haesebrouck, Bram Flahou, Eric Tartour, Darren R Flower, David F Tough, Jagadeesh Bayry
Adjuvants are substances that boost the protective immune response to vaccine antigens. The majority of known adjuvants have been identified through the use of empirical approaches. Our aim was to identify novel adjuvants with well-defined cellular and molecular mechanisms by combining a knowledge of immunoregulatory mechanisms with an in silico approach. CD4(+)CD25(+)FoxP3(+) regulatory T cells (Tregs) inhibit the protective immune responses to vaccines by suppressing the activation of antigen presenting cells such as dendritic cells (DCs)...
2017: Methods in Molecular Biology
Anikó Kapitány, Gabriella Béke, Georgina Nagy, Quang Minh Doan-Xuan, Zsolt Bacso, Krisztián Gáspár, Gábor Boros, Zsolt Dajnoki, Tamás Bíró, Éva Rajnavölgyi, Andrea Szegedi
Skin dendritic cells of patients with atopic dermatitis (AD) are well characterized, but less is known about their peripheral blood precursors. The aim of this study was to investigate the phenotypic features and chemokine production of myeloid pre-dendritic cells of patients with AD ex vivo and after stimulation with Staphylococcus enterotoxin B and thymic stromal lymphopoietin, representing an AD-like microenvironment. The expression of cell surface markers was measured by flow cytometry, while chemokine production was monitored with chemokine antibody array and confirmed by enzyme-linked immunoassays...
October 4, 2016: Acta Dermato-venereologica
Weina Zhang, Lechuang Chen, Kai Ma, Yahui Zhao, Xianghe Liu, Yu Wang, Mei Liu, Shufang Liang, Hongxia Zhu, Ningzhi Xu
Epidermal growth factor receptor (EGFR) is a target of colon cancer therapy, but the effects of this therapy on the tumor microenvironment remain poorly understood. Our in vivo studies showed that cetuximab, an anti-EGFR monoclonal antibody, effectively inhibited AOM/DSS-induced, colitis-associated tumorigenesis, downregulated M2-related markers, and decreased F4/80+/CD206+ macrophage populations. Treatment with conditioned medium of colon cancer cells increased macrophage expression of the M2-related markers arginase-1 (Arg1), CCL17, CCL22, IL-10 and IL-4...
September 23, 2016: Oncotarget
Suzi Hong, Ellen E Lee, Averria Sirkin Martin, Benchawanna Soontornniyomkij, Virawudh Soontornniyomkij, Cristian L Achim, Chase Reuter, Michael R Irwin, Lisa T Eyler, Dilip V Jeste
Chemokines are promising biomarkers of immune activation and inflammation, but evidence for chemokine abnormalities in schizophrenia and their relationship to clinical factors remains inconclusive. We aimed to understand chemokine-related diagnostic differences and clinical correlates using a comprehensive panel and studying a large, well-characterized sample of adults with and without schizophrenia. We studied 134 outpatients with schizophrenia or schizoaffective disorder and 112 healthy comparison (HC) individuals, 26 to 65years of age...
September 17, 2016: Schizophrenia Research
Starlee Lively, Sarah Hutchings, Lyanne C Schlichter
Within hours after stroke, potentially cytotoxic pro-inflammatory mediators are elevated within the brain; thus, one potential therapeutic strategy is to reduce them and skew the brain toward an anti-inflammatory state. Because interleukin-4 (IL-4) treatment induces an anti-inflammatory, "alternative-activation" state in microglia and macrophages in vitro, we tested the hypothesis that early supplementation of the brain with IL-4 can shift it toward an anti-inflammatory state and reduce damage after transient focal ischemia...
September 15, 2016: Journal of Neuropathology and Experimental Neurology
Jared Klarquist, Kristen Tobin, Peyman Farhangi Oskuei, Steven W Henning, Manuel F Fernandez, Emilia R Dellacecca, Flor C Navarro, Jonathan M Eby, Shilpak Chatterjee, Shikhar Mehrotra, Joseph I Clark, I Caroline Le Poole
T regulatory cells (Treg) avert autoimmunity but their increased levels in melanoma confer a poor prognosis. To explore the basis for Treg accumulation in melanoma, we evaluated chemokine expression in patients. A 5-fold increase was documented in the Treg chemoattractants CCL22 and CCL1 in melanoma-affected skin versus unaffected skin, as accompanied by infiltrating FoxP3+ T cells. In parallel, there was a ~2-fold enhancement in expression of CCR4 in circulating Treg but not T effector cells. We hypothesized that redirecting Treg away from tumors might suppress autoimmune side-effects caused by immune checkpoint therapeutics now used widely in the clinic...
September 12, 2016: Cancer Research
In Jun Yang, Dong-Ung Lee, Heung Mook Shin
Valencene (VAL) isolated from Cyperus rotundus possesses various biological effects such as antiallergic and antimelanogenesis activity. We investigated the effect of VAL on atopic dermatitis (AD) skin lesions and their molecular mechanisms. We topically applied VAL to 1-chloro-2,4-dinitrobenzene (DNCB) sensitized NC/Nga mice. Modified scoring atopic dermatitis index, scratching behavior, and histological/immunohistochemical staining were used to monitor disease severity. RT-PCR, western blotting, and enzyme-linked immunosorbent assay were used to determine the level of IgE, proinflammatory cytokines/chemokines production, and skin barrier proteins expression...
2016: Evidence-based Complementary and Alternative Medicine: ECAM
Martin Glatz, Terry Means, Josef Haas, Allen C Steere, Robert R Müllegger
Little is known about the immunomodulation by tick saliva during a natural tick bite in human skin, the site of the tick-host interaction. We examined the expression of chemokines, cytokines, and leukocyte markers on the mRNA levels and histopathologic changes in human skin biopsies of tick bites (n=37) compared to unaffected skin (n=9). Early tick bite skin lesions (<24 h of tick attachment) were characterized by a predominance of macrophages and dendritic cells, elevated mRNA levels of macrophage chemoattractants (CCL2, CCL3, CCL4) and neutrophil chemoattractants (CXCL1, CXCL8), of the pro-inflammatory cytokine, IL-1β and the anti-inflammatory cytokine, IL-5...
September 13, 2016: Experimental Dermatology
Ju-Hye Yang, Jae-Myung Yoo, Won-Kyung Cho, Jin Yeul Ma
BACKGROUND: Sanguisorbae Radix (SR) is a well-known herbal medicine used to treat inflammatory disease and skin burns in Asia. In addition, it is used to treat many types of allergic skin diseases, including urticaria, eczema, and allergic dermatitis. SR has been reported to exhibit anti-wrinkle, anti-oxidant, and anti-contact dermatitis bioactivities. METHODS: In this study, we investigated the mechanism underlying the anti-inflammatory effects of SR water extract (WSR) using human keratinocyte (HaCaT) cells and BALB/c mouse bone marrow-derived mast cells (BMMCs)...
2016: BMC Complementary and Alternative Medicine
Sjors A Koppes, Richard Brans, Suzana Ljubojevic Hadzavdic, Monique H W Frings-Dresen, Thomas Rustemeyer, Sanja Kezic
OBJECTIVE: The aim of this study was to explore the tape strip sampling technique in the assessment of stratum corneum levels of inflammatory mediators in a clinical trial setting. METHODS: Thirty-eight inflammatory mediators were analyzed by a multiplex-assay in the stratum corneum, collected by adhesive tapes before and after 6 weeks of therapy, in mild and moderate atopic dermatitis (AD) patients (n = 90). Treatment was a ceramide- and magnesium-containing emollient...
2016: International Archives of Allergy and Immunology
Chuanjian Lu, Yu-Qun Zeng, Huazhen Liu, Qingfeng Xie, Shengmei Xu, Kangsheng Tu, Changwei Dou, Zhenhua Dai
BACKGROUND: Achieving long-term cardiac allograft survival without continuous immunosuppression is highly desired in organ transplantation. Studies have shown that Salvia miltiorrhiza, an herb also known as danshen, improves microcirculation and is highly effective in treating coronary heart disease. Our objective is to determine whether tanshinol, an ingredient of danshen, improves cardiac allograft survival. METHODS: Fully vascularized heterotopic heart transplantation was performed using BALB/c mice as donors and C57BL/6 mice as recipients, which were then treated with tanshinol and rapamycin...
July 27, 2016: Journal of Heart and Lung Transplantation
Desta Kassa, Leonie Ran, Wilco de Jager, Theo van den Broek, Ronald Jacobi, Muluberhan Mekonen, Tsehaynesh Messele, Mariëlle C Haks, Tom H M Ottenhoff, Debbie van Baarle
BACKGROUND: Transcriptomic host biomarkers could assist in developing effective diagnostics, vaccines and therapeutics for tuberculosis (TB). However, different biomarkers may be discriminatory in different populations depending on the host and bacillary genetics and HIV infection, and need to be addressed. METHODS: The expression levels of 45 genes that are known to be involved in or affected by TB pathogenesis were analyzed using dual color Reverse Transcriptase Multiplex Ligation-dependent Probe Amplification (dcRT-MLPA) assay in whole blood of 106 HIV positive individuals including active TB patients (TB(+)HIV(+), n = 29), and non TB patients that are tuberculin skin test positive (TST+) (TST(+)HIV(+), n = 26), or TST negative (TST(-)HIV(+), n = 51)...
September 2016: Tuberculosis
Dan Li, Mingyue Duan, Yuan Feng, Lingling Geng, Xiaoqing Li, Wanggang Zhang
Monocytes from patients with systemic juvenile idiopathic arthritis (SJIA) have both features of classical activated M1 and alternatively activated M2 macrophages. An increasing number of studies have indicated that microRNAs (miRNAs) are critical regulators of monocyte polarization. Here, we focused on miR-146a expression in SJIA and investigated the function of miR-146a in monocyte polarization. We found that miR-146a expression was highly up-regulated in SJIA monocytes and correlated with the systemic features...
September 2016: Molecular Immunology
J L Cameron, R Jain, M Rais, A E White, T M Beer, P Kievit, K Winters-Stone, I Messaoudi, O Varlamov
BACKGROUND/OBJECTIVES: Androgen deprivation therapy (ADT) is commonly used for treatment of prostate cancer, but is associated with side effects such as sarcopenia and insulin resistance. The role of lifestyle factors such as diet and exercise on insulin sensitivity and body composition in testosterone-deficient males is poorly understood. The aim of the present study was to examine the relationships between androgen status, diet, and insulin sensitivity. SUBJECTS/METHODS: Middle-aged (11-12-yo) intact and orchidectomized male rhesus macaques were maintained for two months on a standard chow diet, and then exposed for six months to a Western-style, high-fat/calorie-dense diet (WSD) followed by four months of caloric restriction (CR)...
August 18, 2016: International Journal of Obesity: Journal of the International Association for the Study of Obesity
Yetrib Hathout, Laurie S Conklin, Haeri Seol, Heather Gordish-Dressman, Kristy J Brown, Lauren P Morgenroth, Kanneboyina Nagaraju, Christopher R Heier, Jesse M Damsker, John N van den Anker, Erik Henricson, Paula R Clemens, Jean K Mah, Craig McDonald, Eric P Hoffman
Corticosteroids are extensively used in pediatrics, yet the burden of side effects is significant. Availability of a simple, fast, and reliable biochemical read out of steroidal drug pharmacodynamics could enable a rapid and objective assessment of safety and efficacy of corticosteroids and aid development of corticosteroid replacement drugs. To identify potential corticosteroid responsive biomarkers we performed proteome profiling of serum samples from DMD and IBD patients with and without corticosteroid treatment using SOMAscan aptamer panel testing 1,129 proteins in <0...
2016: Scientific Reports
Agnes Ling, Ida V Lundberg, Vincy Eklöf, Maria L Wikberg, Åke Öberg, Sofia Edin, Richard Palmqvist
Giving strong prognostic information, T-cell infiltration is on the verge of becoming an additional component in the routine clinical setting for classification of colorectal cancer (CRC). With a view to further improving the tools for prognostic evaluation, we have studied how Th1 lymphocyte infiltration correlates with prognosis not only by quantity, but also by subsite, within CRCs with different molecular characteristics (microsatellite instability, CpG island methylator phenotype status, and BRAF and KRAS mutational status)...
January 2016: Journal of Pathology. Clinical Research
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