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IL 17 receptor B

Lirit N Franks, Benjamin M Ford, Toshifumi Fujiwara, Haibo Zhao, Paul L Prather
Selective estrogen receptor modulators (SERMs) target estrogen receptors (ERs) to treat breast cancer and osteoporosis. Several SERMs exhibit anti-cancer activity not related to ERs. To discover novel anti-cancer drugs acting via ER-independent mechanisms, derivatives of the SERM tamoxifen, known as the "ridaifen" compounds, have been developed that exhibit reduced or no ER affinity, while maintaining cytotoxicity. Tamoxifen and other SERMs bind to cannabinoid receptors with moderate affinity. Therefore, ER-independent effects of SERMs might be mediated via cannabinoid receptors...
June 12, 2018: Toxicology and Applied Pharmacology
Jhimmy Talbot, Raphael S Peres, Larissa G Pinto, Rene D R Oliveira, Kalil A Lima, Paula B Donate, Jaqueline R Silva, Bernard Ryffel, Thiago M Cunha, José C Alves-Filho, Foo Y Liew, Paulo Louzada-Junior, Fernando de Queiroz Cunha
BACKGROUND: Epidemiologic studies have highlighted the association of environmental factors with the development and progression of autoimmune and chronic inflammatory diseases. Among the environmental factors, smoking has been associated with increased susceptibility and poor prognosis in rheumatoid arthritis (RA). However, the immune and molecular mechanism of smoking-induced arthritis aggravation remains unclear. The transcription factor aryl hydrocarbon receptor (AHR) regulates the generation of Th17 cells, CD4 T cells linked the development of autoimmune diseases...
June 8, 2018: Arthritis Research & Therapy
Shira Cohen, Faina Barer, Inbal Itzhak, Michael H Silverman, Pnina Fishman
Interleukin-17 and interleukin-23 play major roles in the inflammatory process in psoriasis. The Gi protein-associated A3 adenosine receptor (A3 AR) is known to be overexpressed in inflammatory cells and in peripheral blood mononuclear cells (PBMCs) of patients with autoimmune inflammatory conditions. Piclidenoson, a selective agonist at the A3 AR, induces robust anti-inflammatory effect in psoriasis patients. In this study, we aimed to explore A3 AR expression levels in psoriasis patients and its role in mediating the anti-inflammatory effect of piclidenoson in human keratinocyte cells...
2018: Journal of Immunology Research
Rehab Alnabhan, Ahmed Gaballa, Lisa-Mari Mörk, Jonas Mattsson, Michael Uhlin, Isabelle Magalhaes
BACKGROUND: The use of CD19 chimeric antigen receptor (CAR) T cells to treat B-cell malignancies has proven beneficial. Several groups use serum to produce CD19 CAR T cells. Today, ready-to-use serum-free media that require no addition of serum are commercially available. Therefore, it becomes important to evaluate the production of CD19 CAR T cells with and without the addition of serum. METHODS: T cells from buffy coats were cultured in AIM-V and TexMACS (TM) supplemented with 5% human serum (A5% and TM5%, respectively), and in TM without serum...
May 30, 2018: Cytotherapy
Boris Hügle, Anastasia Schippers, Nadine Fischer, Kim Ohl, Bernd Denecke, Fabio Ticconi, Bas Vastert, Ivan G Costa, Johannes-Peter Haas, Klaus Tenbrock
BACKGROUND: The term systemic juvenile idiopathic arthritis (sJIA) describes an autoinflammatory condition characterized by arthritis and severe systemic inflammation, which in later stages can transform into interleukin (IL)-17-driven autoimmune arthritis. IL-1 antagonists have been used with good efficacy in the early stages of sJIA. METHODS: A whole transcriptome analysis of peripheral blood RNA samples was performed in six patients with sJIA and active systemic disease, before initiating treatment with the IL-1β receptor antagonist anakinra, and after induction of inactive disease, compared with a single-sample control cohort of 21 patients in several clinical stages of sJIA activity...
May 30, 2018: Arthritis Research & Therapy
G Montes Diaz, J Fraussen, B Van Wijmeersch, R Hupperts, V Somers
The effects of dimethyl fumarate (DMF) on the immune system in multiple sclerosis (MS) are not completely elucidated. In this study, an extensive immunophenotypic analysis of innate and adaptive immune cells of DMF-treated MS patients was performed. Peripheral blood immune cell phenotypes were determined using flow cytometry in a follow-up study of 12 MS patients before, after 3 and 12 months of DMF treatment and a cross-sectional study of 25 untreated and 64 DMF-treated MS patients. Direct effects of DMF on B cells were analyzed in vitro...
May 29, 2018: Scientific Reports
C Custodero, R T Mankowski, S A Lee, Z Chen, S Wu, T M Manini, J Hincapie Echeverri, C Sabbà, D P Beavers, J A Cauley, M A Espeland, R A Fielding, S B Kritchevsky, C K Liu, M M McDermott, M E Miller, R P Tracy, A B Newman, W T Ambrosius, M Pahor, S D Anton
Growing evidence suggests chronic low-grade inflammation (LGI) as a possible mechanism underlying the aging process. Some biological and pharmaceutical compounds may reduce systemic inflammation and potentially avert functional decline occurring with aging. The aim of the present meta-analysis was to examine the association of pre-selected interventions on two established biomarkers of inflammation, interleukin-6 (IL-6), and C-reactive protein (CRP) in middle-age and older adults with chronic LGI. We reviewed the literature on potential anti-inflammatory compounds, selecting them based on safety, tolerability, acceptability, innovation, affordability, and evidence from randomized controlled trials...
May 25, 2018: Ageing Research Reviews
Jin-Sil Park, Na-Rae Kim, Mi-Ae Lim, Sung-Min Kim, Sun-Hee Hwang, Kyung-Ah Jung, JeongWon Choi, Sung-Hwan Park, Mi-La Cho
Rheumatoid arthritis (RA) is a systemic autoimmune disease with CD4+ T cell infiltration and hyperplasia of synovial tissues leading to progressive destruction of articular cartilage. In addition to the central role of T cells in the pathogenesis of RA, recent reports have suggested that B cells also contribute to RA. To explore the effects of interleukin (IL)-17 on B cell development and response in excess IL-1 signaling, we generated IL-17 and IL-1 receptor antagonist (IL-1Ra) double-deficient mice via backcrossing IL-17 knockout (KO) and IL-1RaKO mice...
May 24, 2018: Immunology Letters
A Beringer, N Thiam, J Molle, B Bartosch, P Miossec
The proinflammatory cytokines interleukin (IL)-17 and tumour necrosis factor (TNF)-α are targets for treatment in many chronic inflammatory diseases. Here, we examined their role in liver inflammatory response compared to that of IL-6. Human hepatoma cells (HepaRG, Huh7.5 and HepG2 cells) and primary human hepatocytes (PHH) were cultured with IL-6, IL-17 and/or TNF-α. To determine the contribution of the IL-6 pathway in the IL-17/TNF-α-mediated effect, an anti-IL-6 receptor antibody was used. IL-17 and TNF-α increased in synergy IL-6 secretion by HepaRG cells and PHH but not by Huh7...
April 20, 2018: Clinical and Experimental Immunology
William R English, Heather Ireland-Zecchini, Andrew H Baker, Trevor D Littlewood, Martin R Bennett, Gillian Murphy
Over expression of Tissue Inhibitor of Metalloproteinases-3 (TIMP-3) in vascular smooth muscle cells (VSMCs) induces apoptosis and reduces neointima formation occurring after saphenous vein interposition grafting or coronary stenting. In studies to address the mechanism of TIMP-3-driven apoptosis in human VSMCs we find that TIMP-3 increased activation of caspase-8 and apoptosis was inhibited by expression of Cytokine response modifier A (CrmA) and dominant negative FAS-Associated protein with Death Domain (FADD)...
2018: PloS One
Mengjuan Xue, Chenhe Zhao, Chaoyang Lv, Minling Chen, Ming Xu, Ruiming Rong, Yao Zhang, Jing Liang, Jian Gao, Mingxiang Yu, Tongyu Zhu, Xin Gao
BACKGROUND: The aim of the present study was to examine the association between interleukin-2 receptor antagonists (IL-2Ra) and new-onset diabetes after transplantation (NODAT) among renal transplant recipients (RTRs). METHODS: Between January 1993 and March 2014, 915 patients underwent renal transplantation at Zhongshan Hospital. In all, 557 RTRs were included in the present retrospective cohort study. The incidence of NODAT in this cohort was determined and multivariate Cox regression analysis was used to evaluate the risk factors for NODAT and to show the association between IL-2Ra use and NODAT development among RTRs...
March 25, 2018: Journal of Diabetes
A N Kazimirskii, G V Poryadin, Zh M Salmasi, L Yu Semenova
Tissue damage in various diseases, hypoxic conditions, and some pathologies are associated with production of endogenous factors such as the soluble form of the surface receptor CD100, malonic dialdehyde, and arginase and their release into circulation. These factors modulate functional state of lymphocytes in the immune system: potentiate activation of B lymphocytes, activate synthesis and secretion of IL-25 and IL-17 cytokines, and suppress proliferative activity of T lymphocytes, thus modulating immunological reactivity of the organism...
March 2018: Bulletin of Experimental Biology and Medicine
Cheleka A M Mpande, One B Dintwe, Munyaradzi Musvosvi, Simbarashe Mabwe, Nicole Bilek, Mark Hatherill, Elisa Nemes, Thomas J Scriba
Background: Maintenance of long-lasting immunity is thought to depend on stem cell memory T cells (TSCM ), which have superior self-renewing capacity, longevity and proliferative potential compared with central memory (TCM ) or effector (TEFF ) T cells. Our knowledge of TSCM derives primarily from studies of virus-specific CD8+ TSCM . We aimed to determine if infection with Mycobacterium tuberculosis ( M. tb ), the etiological agent of tuberculosis, generates antigen-specific CD4+ TSCM and to characterize their functional ontology...
2018: Frontiers in Immunology
Joon Ha Park, Bich Na Shin, Ji Hyeon Ahn, Jeong Hwi Cho, Tae-Kyeong Lee, Jae-Chul Lee, Yong Hwan Jeon, Il Jun Kang, Ki-Yeon Yoo, In Koo Hwang, Choong Hyun Lee, Yoo Hun Noh, Sung-Su Kim, Moo-Ho Won, Jong Dai Kim
Background: Glehnia littoralis has been used for traditional Asian medicine, which has diverse therapeutic activities. However, studies regarding neurogenic effects of G. littoralis have not yet been considered. Therefore, in this study, we examined effects of G. littoralis extract on cell proliferation, neuroblast differentiation, and the maturation of newborn neurons in the hippocampus of adult mice. Methods: A total of 39 male ICR mice (12 weeks old) were randomly assigned to vehicle-treated and 100 and 200 mg/kg G...
March 20, 2018: Chinese Medical Journal
Chris Schiering, Anne Vonk, Srustidhar Das, Brigitta Stockinger, Emma Wincent
The aryl hydrocarbon receptor (AHR) controls interleukin 22 production by T helper 17 cells (Th17). IL-22 contributes to intestinal homeostasis but has also been implicated in chronic inflammatory disorders and colorectal cancer, highlighting the need for appropriate regulation of IL-22 production. Upon activation, the AHR induces expression of cytochrome P4501 (CYP1) enzymes which in turn play an important feedback role that curtails the duration of AHR signaling by metabolizing AHR ligands. Recently we described how agents that inhibit CYP1 function potentiate AHR signaling by disrupting metabolic clearance of the endogenous ligand 6-formylindolo[3,2-b]carbazole (FICZ)...
May 2018: Biochemical Pharmacology
Luiz E B Savio, Paola de Andrade Mello, Cleide Gonçalves da Silva, Robson Coutinho-Silva
Under physiological conditions, adenosine triphosphate (ATP) is present at low levels in the extracellular milieu, being massively released by stressed or dying cells. Once outside the cells, ATP and related nucleotides/nucleoside generated by ectonucleotidases mediate a high evolutionary conserved signaling system: the purinergic signaling, which is involved in a variety of pathological conditions, including inflammatory diseases. Extracellular ATP has been considered an endogenous adjuvant that can initiate inflammation by acting as a danger signal through the activation of purinergic type 2 receptors-P2 receptors (P2Y G-protein coupled receptors and P2X ligand-gated ion channels)...
2018: Frontiers in Pharmacology
K L Winthrop, X Mariette, J T Silva, E Benamu, L H Calabrese, A Dumusc, J S Smolen, J M Aguado, M Fernández-Ruiz
BACKGROUND: The present review is part of the ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies. AIMS: To review, from an Infectious Diseases perspective, the safety profile of agents targeting interleukins, immunoglobulins and complement factors and to suggest preventive recommendations. SOURCES: Computer-based MEDLINE searches with MeSH terms pertaining to each agent or therapeutic family...
February 12, 2018: Clinical Microbiology and Infection
Zhongxiu Wang, Jingyi Tan, Lihong Lei, Weilian Sun, Yanmin Wu, Peihui Ding, Lili Chen
OBJECTIVE: Interleukin-17 (IL-17) and interferon-gamma (IFN-γ) are all pro-inflammatory cytokines produced by specific subsets of T-cells and are also considered crucial regulators in bone remodeling, but their effects on osteogenesis have not been carefully studied. So, this study aimed to investigate the effects of secreting cytokines IL-17 and IFN-γ on the osteogenesis of primary osteoblasts and to clarify the potential roles of the related Janus activated kinase 2 (JAK2) and downstream signal transducer and activator of transcription 3 (STAT3) signaling pathway in bone remodeling...
April 2018: International Immunopharmacology
David G Hill, Liang Yu, Hugh Gao, Jesse J Balic, Alison West, Hiroko Oshima, Louise McLeod, Masanobu Oshima, Awen Gallimore, Kimberley D'Costa, Prithi S Bhathal, William Sievert, Richard L Ferrero, Brendan J Jenkins, Gareth W Jones
Tertiary lymphoid structures (TLSs) display phenotypic and functional characteristics of secondary lymphoid organs, and often develop in tissues affected by chronic inflammation, as well as in certain inflammation-associated cancers where they are prognostic of improved patient survival. However, the mechanisms that govern the development of tumour-associated TLSs remain ill-defined. Here, we observed tumour-associated TLSs in a preclinical mouse model (gp130F/F ) of gastric cancer, where tumourigenesis is dependent on hyperactive STAT3 signalling through the common IL-6 family signalling receptor, gp130...
July 1, 2018: International Journal of Cancer. Journal International du Cancer
Priyanka Shukla, Mohd Nizam Mansoori, Divya Singh
Recent studies have identified that Interleukin (IL)-23/IL-17 axis plays crucial role in pathogenesis of inflammation and bone destruction. IL-23 is thought to promote joint destruction in arthritis by stimulating Th17 cells. IL-23 directly mediates bone loss by inducing osteoclastogenesis and receptor activator of kappa B ligand (RANKL) expression in T cells. IL-23 also promotes tartrate-resistant acid phosphatase (TRAP) activity of osteoclast in osteoblast-osteoclast co-culture. The role of IL-23 has not been studied in estrogen deficiency induced bone loss...
May 2018: Bone
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