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https://www.readbyqxmd.com/read/27905107/co-operative-suppression-of-inflammatory-responses-in-human-dendritic-cells-by-plant-proanthocyanidins-and-products-from-the-parasitic-nematode-trichuris-suis
#1
Andrew R Williams, Elsenoor J Klaver, Lisa C Laan, Aina Ramsay, Christos Fryganas, Rolf Difborg, Helene Kringel, Jess D Reed, Irene Mueller-Harvey, Søren Skov, Irma van Die, Stig M Thamsborg
Interactions between dendritic cells (DCs) and environmental, dietary and pathogen antigens play a key role in immune homeostasis and regulation of inflammation. Dietary polyphenols such as proanthocyanidins (PAC) may reduce inflammation, and we therefore hypothesized that PAC may suppress lipopolysaccharide (LPS) -induced responses in human DCs and subsequent T helper type 1 (Th1) -type responses in naive T cells. Moreover, we proposed that, because DCs are likely to be exposed to multiple stimuli, the activity of PAC may synergise with other bioactive molecules that have anti-inflammatory activity, e...
November 7, 2016: Immunology
https://www.readbyqxmd.com/read/27898346/amp-kinase-promotes-bcl6-expression-in-both-mouse-and-human-t-cells
#2
Markus M Xie, Tohti Amet, Hong Liu, Qigui Yu, Alexander L Dent
The transcription factor Bcl6 is a master regulator of follicular helper T (TFH) cells, and understanding the signaling pathway that induces Bcl6 and TFH cell differentiation is therefore critical. IL-2 produced during T cell activation inhibits Bcl6 expression but how TFH cells evade IL-2 inhibition is not completely understood. Here we show that Bcl6 is highly up-regulated in activated CD4 T cells following glucose deprivation (GD), and this pathway is insensitive to inhibition by IL-2. Similar to GD, the glucose analog 2-deoxyglucose (2DG) inhibits glycolysis, and 2DG induced Bcl6 expression in activated CD4 T cells...
November 26, 2016: Molecular Immunology
https://www.readbyqxmd.com/read/27852111/ror%C3%AE-t-inhibitors-as-potential-back-ups-for-the-phase-ii-candidate-vtp-43742-from-vitae-pharmaceuticals-patent-evaluation-of-wo2016061160-and-us20160122345
#3
Christian Gege
Retinoic acid receptor-related orphan nuclear receptor gamma t (RORγt or RORc2) is a key transcription factor for the differentiation of naïve proinflammatory CD4(+) T cells and the production of T helper-17 (TH17) cells. Inhibiting RORγt activity is thought to be beneficial in targeting a variety of inflammatory and autoimmune disorders. Recently Vitae Pharmaceuticals (to be acquired by Allergan) reported positive top-line results from a Phase 2a clinical trial of RORγt inhibitor VTP-43742 in psoriatic patients...
November 17, 2016: Expert Opinion on Therapeutic Patents
https://www.readbyqxmd.com/read/27756053/costunolide-a-sesquiterpene-lactone-inhibits-the-differentiation-of-pro-inflammatory-cd4-t-cells-through-the-modulation-of-mitogen-activated-protein-kinases
#4
Eunchong Park, Ju Han Song, Myun Soo Kim, Su-Ho Park, Tae Sung Kim
CD4(+) T cell activation and adequate differentiation into effector T helper (Th) cells are crucial for mediating adaptive immune responses to cope with foreign pathogens. Despite the significant role of Th cells, excessive increases in their numbers result in inflammatory and autoimmune diseases. In this study, we investigated the effects of costunolide, a plant-derived natural compound with an anti-inflammatory activity, in regulating Th cells and the underlying mechanisms. Costunolide significantly decreased cell populations of differentiated Th1, Th2, and Th17 subsets under Th subset-polarizing conditions, while exerting statistically negligible effects on Treg cell differentiation...
October 15, 2016: International Immunopharmacology
https://www.readbyqxmd.com/read/27751819/a-fumigaclavine-c-isostere-alleviates-th1-mediated-experimental-colitis-via-competing-with-ifn-%C3%AE-for-binding-to-ifn-%C3%AE-receptor-1
#5
Yang Tan, Xingxin Wu, Jing Sun, Wenjie Guo, Fangyuan Gong, Fenli Shao, Tao Tan, Yi Cao, Bingfeng Zheng, Yanhong Gu, Yang Sun, Qiang Xu
Interferon gamma (IFN-γ) signaling in T cells plays an important role in developing T helper 1 (Th1)-mediated inflammation. Selective regulation of IFN-γ signaling is an attractive strategy for treating Th1-mediated immune diseases. In this study, we aimed to explore possible means of targeting IFN-γ signaling by using small molecule compound. A synthetic small molecule FC9 was identified as it selectively inhibited IFN-γ signaling in T cells without suppressing interleukin 4 (IL-4) signaling. Furthermore, FC9 inhibited IFN-γ-induced Janus kinase 2 (JAK2) activation via competing with IFN-γ for binding to IFN-γ receptor 1 (IFN-γ R1)...
October 14, 2016: Biochemical Pharmacology
https://www.readbyqxmd.com/read/27746240/protein-kinase-c%C3%AE-controls-type-2-innate-lymphoid-cell-and-th2-responses-to-house-dust-mite-allergen
#6
Fahima Madouri, Pauline Chenuet, Chloé Beuraud, Louis Fauconnier, Tiffany Marchiol, Nathalie Rouxel, Aurélie Ledru, Margaux Gallerand, Vincent Lombardi, Laurent Mascarell, Quentin Marquant, Lionel Apetoh, François Erard, Marc Le Bert, Fabrice Trovero, Valérie F J Quesniaux, Bernhard Ryffel, Dieudonnée Togbe
BACKGROUND: Protein kinase C (PKC) θ, a serine/threonine kinase, is involved in TH2 cell activation and proliferation. Type 2 innate lymphoid cells (ILC2s) resemble TH2 cells and produce the TH2 cytokines IL-5 and IL-13 but lack antigen-specific receptors. The mechanism by which PKC-θ drives innate immune cells to instruct TH2 responses in patients with allergic lung inflammation remains unknown. OBJECTIVES: We hypothesized that PKC-θ contributes to ILC2 activation and might be necessary for ILC2s to instruct the TH2 response...
October 14, 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27697049/macrolide-hybrid-compounds-drug-discovery-opportunities-in-anti-infective-and-anti-inflammatory-area
#7
Hana Čipčić Paljetak, Linda Tomašković, Mario Matijašić, Mirjana Bukvić, Andrea Fajdetić, Donatella Verbanac, Mihaela Perića
5-LOX - 5-lipoxygenase; ACT - artemisinin-based combination therapies; ADME - absorption, distribution, metabolism and excretion; BAL - broncho alveolar lavage; CABP - community acquired bacterial pneumonia; cAMP - cyclic adenosine monophosphate; CAP - community-acquired pneumonia; CF - cystic fibrosis, BOS bronchiolitis obliterans syndrome; cGMP - cyclic guanosine monophosphate; COPD - chronic obstructive pulmonary disease; COX - cyclooxygenase; DPB - diffuse panbronchiolitis; HDACs - histone deacetylases; IBD - inflammatory bowel disease; IL-1p - interleukin 1p; IL-6 - interleukin 6; MIC - minimal inhibitory concentrations; MLSB - macrolide, lincosamide, streptogramin B; NSAIDs - non-steroidal anti-inflammatory drugs; OVA - ovalbumin; PDE4 - phosphodiesterase 4; PMA - phorbol 12-myristate 13-acetate; RA - rheumatoid arthritis; RTI - respiratory tract infections; SAHA - suberoylanilide hydroxamic acid; SAR - structure-activity-relationship; Th1 - type 1 helper T-cell; TNBS - trinitrobenzene sulfonic acid; TNF-α - tumour necrosis factor α; UN - United Nations, WHO - World Health Organisation...
September 27, 2016: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/27696392/interleukin-17-as-a-factor-linking-the-pathogenesis-of-psoriasis-with-metabolic-disorders
#8
Agnieszka Owczarczyk-Saczonek, Waldemar Placek
Psoriasis is a systemic disease with numerous concomitant metabolic disorders. Apparently, T-helper 17 lymphocytes and interleukin (IL)-17 constitute an important element linking those disorders. The role of IL-17 has been confirmed by numerous studies, although it remains not completely understood, and the study results are controversial. Based on the studies performed so far, it is assumed that IL-17 contributes to development of atherosclerosis by means of: stimulation of production of proinflammatory compounds; induction of apoptosis of endothelial cells and heart muscle cells; stimulation of von Willebrand factor production; and induction of the matrix metalloproteinase-9 (atherosclerotic plaque rupture)...
October 1, 2016: International Journal of Dermatology
https://www.readbyqxmd.com/read/27574849/rosae-multiflorae-fructus-hot-water-extract-inhibits-a-murine-allergic-asthma-via-the-suppression-of-th2-cytokine-production-and-histamine-release-from-mast-cells
#9
Chang Ho Song, Thi Tho Bui, Chun Hua Piao, Hee Soon Shin, Dong-Hwa Shon, Eui-Hyeog Han, Hyoung Tae Kim, Ok Hee Chai
Mast cell-mediated anaphylactic reactions are involved in many allergic diseases, including asthma and allergic rhinitis. In Korea, where it has been used as a traditional medicine, Rosae Multiflorae fructus (RMF) is known to have potent antioxidative, analgesic, and anti-inflammatory activities and to have no obvious acute toxicity. However, its specific effect on asthma is still unknown. In this study, we evaluated whether or not RMF hot water extracts (RMFW) could inhibit ovalbumin (OVA)-induced allergic asthma and evaluated compound 48/80-induced mast cell activation to elucidate the mechanisms of asthma inhibition by RMFW...
September 2016: Journal of Medicinal Food
https://www.readbyqxmd.com/read/27562088/6-shogaol-an-active-compound-of-ginger-alleviates-allergic-dermatitis-like-skin-lesions-via-cytokine-inhibition-by-activating-the-nrf2-pathway
#10
Gunhyuk Park, Dal-Seok Oh, Mi Gi Lee, Chang Eon Lee, Yong-Ung Kim
Allergic dermatitis (AD) clinically presents with skin erythematous plaques, eruption, and elevated serum IgE, and T helper cell type 2 and 1 (Th2 and Th1) cytokine levels. 6-Shogaol [1-(4-hydroxy-methoxyphenyl)-4-decen-one], a pungent compound isolated from ginger, has shown anti-inflammatory effects, but its inhibitory effects on AD are unknown. The aim of this study was to examine whether 6-shogaol inhibits AD-like skin lesions and their underlying mechanism in vivo and in vitro. An AD-like response was induced by tumor necrosis factor-α (TNF-α)+IFN-γ in human keratinocytes or by 2,4-dinitrochlorobenzene (DNCB) in mice...
November 1, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/27513008/human-toll-like-receptor-tlr-8-specific-agonistic-activity-in-substituted-pyrimidine-2-4-diamines
#11
Mallesh Beesu, Alex C D Salyer, Kathryn L Trautman, Justin K Hill, Sunil A David
Activation of human toll-like receptor-8 (TLR8) evokes a distinct cytokine profile favoring the generation of Type 1 helper T cells. A multiplexed high-throughput screen had led to the identification of N(4)-butyl-5-iodo-6-methylpyrimidine-2,4-diamine as a pure TLR8 agonist, and a detailed structure-activity relationship study of this chemotype was undertaken. A butyl substituent at N(4) was optimal, and replacement of the 5-iodo group with chloro, bromo, or fluoro groups led to losses in potency, as did the introduction of aromatic bulk...
September 8, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27497749/children-s-white-blood-cell-counts-in-relation-to-developmental-exposures-to-methylmercury-and-persistent-organic-pollutants
#12
Y Oulhote, Z Shamim, K Kielsen, P Weihe, P Grandjean, L P Ryder, C Heilmann
BACKGROUND: To explore possible markers of developmental immunotoxicity, we prospectively examined 56 children to determine associations between exposures to methylmercury and persistent organic pollutants since birth and the comprehensive differential counts of white blood cells (WBC) at age 5 years. MATERIALS AND METHODS: Extended differential count included: neutrophils, eosinophils, basophils, lymphocytes (includingT cells, NK cells, and B cells), and monocytes...
August 4, 2016: Reproductive Toxicology
https://www.readbyqxmd.com/read/27458225/a-high-throughput-approach-to-identify-compounds-that-impair-envelope-integrity-in-escherichia-coli
#13
Kristin R Baker, Bimal Jana, Henrik Franzyk, Luca Guardabassi
The envelope of Gram-negative bacteria constitutes an impenetrable barrier to numerous classes of antimicrobials. This intrinsic resistance, coupled with acquired multidrug resistance, has drastically limited the treatment options against Gram-negative pathogens. The aim of the present study was to develop and validate an assay for identifying compounds that increase envelope permeability, thereby conferring antimicrobial susceptibility by weakening of the cell envelope barrier in Gram-negative bacteria. A high-throughput whole-cell screening platform was developed to measure Escherichia coli envelope permeability to a β-galactosidase chromogenic substrate...
October 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27435207/cpa-7-influences-immune-profile-and-elicits-anti-prostate-cancer-effects-by-inhibiting-activated-stat3
#14
Meihua Liang, Fei Zhan, Juan Zhao, Qi Li, Jiazi Wuyang, Guannan Mu, Dianjun Li, Yanqiao Zhang, Xiaoyi Huang
BACKGROUND: Platinum-based chemotherapy is emerging as the first line of treatment for castration resistant prostate cancer. Among the family of platinum (IV)-based compounds, a member known as CPA-7 inhibits the growth of multiple cancer cell lines. However, how and to what extent CPA-7 elicits its anti-prostate cancer effects in vivo is largely unknown. METHODS: In this study, we firstly assessed the potential toxicity of the synthesized CPA-7 in a prostate cancer model as well as in normal mice...
2016: BMC Cancer
https://www.readbyqxmd.com/read/27419854/a-multi-objective-compounded-local-mobile-cloud-architecture-using-priority-queues-to-process-multiple-jobs
#15
Xiaohui Wei, Bingyi Sun, Jiaxu Cui, Gaochao Xu
As a result of the greatly increased use of mobile devices, the disadvantages of portable devices have gradually begun to emerge. To solve these problems, the use of mobile cloud computing assisted by cloud data centers has been proposed. However, cloud data centers are always very far from the mobile requesters. In this paper, we propose an improved multi-objective local mobile cloud model: Compounded Local Mobile Cloud Architecture with Dynamic Priority Queues (LMCpri). This new architecture could briefly store jobs that arrive simultaneously at the cloudlet in different priority positions according to the result of auction processing, and then execute partitioning tasks on capable helpers...
2016: PloS One
https://www.readbyqxmd.com/read/27405485/control-of-autoimmune-inflammation-by-celastrol-a-natural-triterpenoid
#16
Shivaprasad H Venkatesha, Steven Dudics, Brian Astry, Kamal D Moudgil
Celastrol is a bioactive compound derived from traditional Chinese medicinal herbs of the Celastraceae family. Celastrol is known to possess anti-inflammatory and anti-oxidant activities. Our studies have highlighted the immunomodulatory attributes of celastrol in adjuvant-induced arthritis (AA), an experimental model of human rheumatoid arthritis (RA). RA is an autoimmune disease characterized by chronic inflammation of the synovial lining of the joints, leading eventually to tissue damage and deformities...
August 2016: Pathogens and Disease
https://www.readbyqxmd.com/read/27392200/cytokines-related-to-three-major-types-of-cell-mediated-immunity-in-short-and-long-term-exposures-to-lead-compounds
#17
Michał Dobrakowski, Marta Boroń, Zenon P Czuba, Aleksandra Kasperczyk, Anna Machoń-Grecka, Sławomir Kasperczyk
Many investigators have posited on the significant influence of lead on the immune system function. However, available data on this topic are not conclusive. Therefore, a study was undertaken to examine associations between lead exposure and levels of cytokines related to the T-helper (TH)-1, TH2, and TH17 types of immune response in humans. For these analyses, three population groups were examined: the first consisted of male workers exposed to lead for a short period of time (36-44 days); the second included male workers chronically exposed to lead (13 ± 10 years); and a control group that was composed of male administrative workers with blood lead levels (BLL) < 10 μg/dl...
July 8, 2016: Journal of Immunotoxicology
https://www.readbyqxmd.com/read/27317944/pharmacological-characterization-of-crth2-antagonist-las191859-long-receptor-residence-time-translates-into-long-lasting-in-vivo-efficacy
#18
Marta Calbet, Miriam Andrés, Clara Armengol, Mónica Bravo, Peter Eichhorn, Rosa López, Vicente García-González, Richard Roberts, Montserrat Miralpeix
The chemoattractant receptor-homologous molecule expressed on T-helper type 2 cells (CRTh2) is a G protein-coupled receptor expressed on the leukocytes most closely associated with asthma and allergy like eosinophils, mast cells, Th2-lymphocytes and basophils. At present it is clear that CRTh2 mediates most prostaglandin D2 (PGD2) pro-inflammatory effects and as a result antagonists for this receptor have reached asthma clinical studies showing a trend of lung function improvement. The challenge remains to identify compounds with improved clinical efficacy when administered once a day...
September 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/27221314/influence-of-different-types-of-contact-hypersensitivity-on-imiquimod-induced-psoriasis-like-inflammation-in-mice
#19
Shuang Bai, Zhenying Zhang, Suchun Hou, Xiaoming Liu
It is currently believed that psoriasis and allergic contact dermatitis (ACD) are different diseases; however, they share clinical similarities. The involvement of T helper 17 (Th17) cells in these disorders provides a novel opportunity to investigate the relationship between them. The present study aimed to determine whether the same or overlapping inflammatory pathways are involved in the two diseases, and the influence of different types of ACD on psoriasis. Compound mouse models of Th1 or Th2‑type contact hypersensitivity (CHS) combined with imiquimod (IMQ)‑induced psoriasis‑like inflammation were established, in order to mimic the characteristics of ACD and psoriasis...
July 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27184577/di-peptide-modified-gemini-surfactants-as-gene-delivery-vectors-exploring-the-role-of-the-alkyl-tail-in-their-physicochemical-behavior-and-biological-activity
#20
Mays A Al-Dulaymi, Jackson M Chitanda, Waleed Mohammed-Saeid, Hessamaddin Younesi Araghi, Ronald E Verrall, Pawel Grochulski, Ildiko Badea
The aim of this work was to elucidate the structure-activity relationship of new peptide-modified gemini surfactant-based carriers. Glycyl-lysine modified gemini surfactants that differ in the length and degree of unsaturation of their alkyl tail were used to engineer DNA nano-assemblies. To probe the optimal nitrogen to phosphate (N/P) ratio in the presence of helper lipid, in vitro gene expression and cell toxicity measurements were carried out. Characterization of the nano-assemblies was accomplished by measuring the particle size and surface charge...
September 2016: AAPS Journal
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