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A A Alshevskaya, F D Kireev, Z A Laushkina, J A Lopatnikova, V S Gladkikh, J A Sennikova, A V Karaulov, S V Sennikov
BACKGROUND: Tumour necrosis factor-alpha (TNF-α) and its inhibitors are involved in both defence against tuberculosis (TB) and damage to the host by TB. Notably, the change in receptor expression on cell density is a key mechanism in regulation of the biological properties of cytokines. OBJECTIVE: To study the differences in TNF-α receptor (TNFR) expression in patients with active pulmonary tuberculosis (aPTB) in correlation with the parameters of disease severity...
February 1, 2018: International Journal of Tuberculosis and Lung Disease
Manikandan Samidurai, Vijay S Ramasamy, Jihoon Jo
Objective The suppressive action of the acute application of oligomeric amyloid-β (Aβ) on hippocampal long-term potentiation (LTP) has been reported widely. Many mechanisms have been proposed for Aβ inhibited LTP induction. The inflammatory cytokine tumor necrosis factor-α (TNF-α) has also been reported to play a key role in this LTP inhibition through Aβ. However, the underlying molecular mechanisms are largely unknown. This study aimed to investigate the link between Aβ- and TNF-α-mediated hippocampal LTP inhibition...
February 20, 2018: Neurological Research
Cristina Municio, Ángeles Dominguez-Soto, Sara Fuentelsaz-Romero, Amalia Lamana, Nuria Montes, Víctor D Cuevas, Raquel García Campos, José L Pablos, Isidoro González-Álvaro, Amaya Puig-Kröger
OBJECTIVES: Methotrexate (MTX) is the anchor drug for treatment of rheumatoid arthritis (RA), but the mechanism of its anti-inflammatory action is not fully understood. In RA, macrophages display a proinflammatory polarisation profile that resembles granulocyte-macrophage colony-stimulating factor (GM-CSF)-differentiated macrophages and the response to MTX is only observed in thymidylate synthase+ GM-CSF-dependent macrophages. To determine the molecular basis for the MTX anti-inflammatory action, we explored toll-like receptor (TLR), RA synovial fluid (RASF) and tumour necrosis factor receptor (TNFR)-initiated signalling in MTX-exposed GM-CSF-primed macrophages...
February 3, 2018: Annals of the Rheumatic Diseases
Qing-Zeng Qian, Xiang-Ke Cao, Hai-Yan Liu, Guo-Ying Zheng, Qing-Qiang Qian, Fu-Hai Shen
We explored the role of TNFR/TNF-α signalingin apoptosis among alveolar macrophages (AM) and its relevance to the development of coal workers' pneumoconiosis (CWP). Purified alveolar macrophages (AMs) were prepared from bronchoalveolar lavage fluid harvested from 366 CWP patients and 120 healthy subjects enrolled inthe study. The purified AMs were then divided into control, SOD, anti-TNFR, TNFR and NFkB inhibitor groups and analyzed for apoptosis usingflow cytometry (sub-diploid peak) and western blotting (Bcl-2, Caspase-3 and Caspase-8 expression)...
January 2, 2018: Oncotarget
Othman Montacir, Houda Montacir, Andreas Springer, Stephan Hinderlich, Fereidoun Mahboudi, Amirhossein Saadati, Maria Kristina Parr
Etanercept is a soluble fusion protein of the tumor necrosis factor receptor (TNFR) extracellular domain, linked to an Fc part of IgG1. It possesses three N- and 13 O-glycosylation sites. Due to its complex structure, an analytical challenge is facing the development and approval of biosimilars. In the current study, physicochemical characterization using state-of-the-art analytics was performed to analyze intact and subunit masses, post-translational modifications (PTMs), higher order structure and potency of Etanercept originator Enbrel® and its biosimilar Altebrel™ (AryoGen Pharmed) in accordance to critical quality attributes of biopharmaceuticals...
February 6, 2018: Protein Journal
Sudhir Gupta, Houfen Su, Sudhanshu Agrawal, Sastry Gollapudi
Background: Progressive T cell decline in aged humans is associated with a deficiency of naïve (TN) and central memory (TCM) T cells. We have previously reported increased Tumor necrosis factor-α (TNF-α)-induced apoptosis in TN and TCM T cells in aged humans; however, the molecular basis of increased apoptosis remains to be defined. Since expression of TNF receptors (TNFRs) was reported to be comparable in young and aged, we investigated signaling events downstream of TNFRs to understand the molecular basis of increased TNF-α-induced apoptosis in aged TN and TCM CD8+ cells...
2018: Immunity & Ageing: I & A
Alice Borghi, Mira Haegman, Roman Fischer, Isabelle Carpentier, Mathieu J M Bertrand, Claude Libert, Inna S Afonina, Rudi Beyaert
Tumor Necrosis Factor (TNF) is a proinflammatory cytokine that elicits its action by binding to two cell surface TNF receptors (TNFR), TNFR1 and TNFR2, which are expressed by many different cell types. Stimulation of TNFR1 activates canonical NF-κB signaling, leading to the NF-κB dependent expression of a large number of genes. Canonical NF-κB signaling requires the assembly of a TNFR1 signaling complex at the cell membrane, whose formation is regulated by different protein ubiquitination events. In this context, recruitment of the Linear Ubiquitin Chain Assembly Complex (LUBAC) to TNFR1 plays an important role by mediating M1-linked polyubiquitination of specific NF-κB signaling proteins...
January 26, 2018: Biochemical Pharmacology
Zhigang Rong, Fei Zhang, Zhengdong Wang, Weifeng He, Shi-Wu Dong, Jianzhong Xu, Fei Dai
Use of allogeneic mesenchymal stem cells (allo-MSCs) in bone tissue engineering strategies can overcome the limitations associated with autologous MSCs, but unfortunately, the immunogenicity of allo-MSCs leads to a high rate of rejection, unless immunosuppressive agents are used. B and T lymphocyte attenuator (BTLA) is a newly discovered immunoglobulin superfamily inhibitory receptor, and Herpesvirus-entry mediator (HVEM), a member of the TNFR family, is the only ligand of BTLA. Both BTLA and HVEM are widely expressed in B and T lymphocytes and other immune cells and play significant roles in the negative regulation of an immunoreaction...
January 27, 2018: Tissue Engineering. Part A
Di Zhang, Brian Whitaker, Mehabaw G Derebe, Mark L Chiu
Immunostimulatory antibodies against the tumor necrosis factor receptors (TNFR) are emerging as promising cancer immunotherapies. The agonism activity of such antibodies depends on crosslinking to Fc gamma RIIB receptor (FcγRIIB) to enable the antibody multimerization that drives TNFR activation. Previously, Fc engineering was used to enhance the binding of such antibodies to Fcγ receptors. Here, we report the identification of Centyrins as alternative scaffold proteins with binding affinities to homologous FcγRIIB and FcγRIIA, but not to other types of Fcγ receptors...
January 23, 2018: MAbs
Aurelia Busca, Yulia Konarski, Niranjala Gajanayaka, Shifawn O'Hara, Jonathan Angel, Maya Kozlowski, Ashok Kumar
The inhibitors of apoptosis (IAP) proteins, initially described in the context of apoptosis regulation as promoting cell survival, have recently emerged as key regulators of innate immune signaling. As a result, downregulation of IAP via Smac mimetics (SMM) has both survival and immunoregulatory effects. IAPs modulate cytokine production in murine models either as a single agent or in response to LPS. However, the role of SMM and the involvement of IAPs in primary human cells and in particular macrophages with respect to cytokine production and innate immune responses remain largely unknown...
January 22, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Sahin Sultana, Biswadev Bishayi
Staphylococcal septic arthritis remains a serious medical concern due to rapid and sustained production of inflammatory cytokines that leads to progressive and irreversible joint destruction with high mortality rate in patients despite adequate antibiotics treatment. TNF-α signalling via TNFR-1 contributes to arthritic destruction by aggravating inflammation. Impact of TNFR-2 signalling is not well established in this aspect. Hence the objective of our study was to evaluate the role of dual neutralization TNFR-1 and TNFR-2 in the pathogenesis of S...
January 12, 2018: Immunology Letters
Payal Mittal, Rebecca Abblett, Joseph M Ryan, Adam T Hagymasi, Archibald Agyekum-Yamoah, Julia Svedova, Steven L Reiner, Marie-Clare St Rose, Matthew P Hanley, Anthony T Vella, Adam J Adler
Agonists to the TNF/TNFR costimulatory receptors CD134 (OX40) and CD137 (4-1BB) elicit antitumor immunity. Dual costimulation with anti-CD134 plus anti-CD137 is particularly potent because it programs cytotoxic potential in CD8+ and CD4+ T cells. Cytotoxicity in dual-costimulated CD4 T cells depends on the T-box transcription factor eomesodermin (Eomes), which we report is induced via a mechanism that does not rely on IL-2, in contrast to CD8+ CTL, but rather depends on the CD8 T cell lineage commitment transcription factor Runx3, which supports Eomes expression in mature CD8+ CTLs...
January 5, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Jian-Lu Wei, Wenyu Fu, Yuan-Jing Ding, Aubryanna Hettinghouse, Matin Lendhey, Ran Schwarzkopf, Oran D Kennedy, Chuan-Ju Liu
BACKGROUND: Atsttrin, an engineered protein composed of three tumor necrosis factor receptor (TNFR)-binding fragments of progranulin (PGRN), shows therapeutic effect in multiple murine models of inflammatory arthritis . Additionally, intra-articular delivery of PGRN protects against osteoarthritis (OA) progression. The purpose of this study is to determine whether Atsttrin also has therapeutic effects in OA and the molecular mechanisms involved. METHODS: Surgically induced and noninvasive rupture OA models were established in mouse and rat, respectively...
December 19, 2017: Arthritis Research & Therapy
Aruna Bitra, Tzanko Doukov, Jing Wang, Gaelle Picarda, Chris A Benedict, Michael Croft, Dirk M Zajonc
4-1BB (CD137) is a TNF receptor superfamily (TNFRSF) member that is thought to undergo receptor trimerization upon binding to its trimeric TNF superfamily ligand (4-1BBL) to stimulate immune responses. 4-1BB also can bind to the tandem repeat-type lectin Galectin-9 (Gal-9), and signaling through mouse (m)4-1BB is reduced in Galectin-9 (Gal-9) deficient mice, suggesting a pivotal role of Gal-9 in m4-1BB activation. Here, using sulfur-SAD phasing, we determined the crystal structure of m4-1BB to 2.2 Å resolution...
December 14, 2017: Journal of Biological Chemistry
Tonya S Orchard, Rebecca R Andridge, Lisa D Yee, Maryam B Lustberg
BACKGROUND: Modifiable lifestyle factors, such as diet quality, could reduce inflammation and improve quality of life (QOL) in breast cancer survivors, but data are inconclusive. OBJECTIVE: To determine whether diet quality, as measured by Healthy Eating Index-2010 (HEI-2010) score, is associated with inflammation, health status, or functional outcomes affecting QOL in survivors of early-stage breast cancer. DESIGN: This is a cross-sectional, secondary analysis of baseline data collected from breast cancer survivors after completion of primary therapy and before random assignment to a pilot nutritional intervention aimed at reducing side effects of aromatase inhibitor treatment...
December 9, 2017: Journal of the Academy of Nutrition and Dietetics
Ji-Hyun Park, Young Ho Seo, Jung-Hee Jang, Chul-Ho Jeong, Sooyeun Lee, Byoungduck Park
BACKGROUND: Methamphetamine (METH) is a commonly abused drug that may result in neurotoxic effects. Recent studies have suggested that involvement of neuroinflammatory processes in brain dysfunction is induced by misuse of this drug. However, the mechanism underlying METH-induced inflammation and neurotoxicity in neurons is still unclear. In this study, we investigated whether asiatic acid (AA) effected METH-mediated neuroinflammation and neurotoxicity in dopaminergic neuronal cells. And we further determined whether the effect involved in the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and signal transducer and activator of transcription (STAT)3 and extracellular signal-regulated kinase (ERK) pathway...
December 11, 2017: Journal of Neuroinflammation
Sahin Sultana, Rajen Dey, Biswadev Bishayi
Severity of S. aureus septic arthritis is correlated to prolonged inflammation by inflammatory cytokines like TNF-α, IL-1β, and IL-6 even after successful elimination of bacteria. Role of TNF-α via TNFR2 is not well established in this aspect. IFN-γ induces TNF-α release from the macrophages augmenting the inflammatory arthritis. IL-10 modulates the levels of pro-inflammatory cytokines promoting resolution of inflammation. TNF-α-TNFR2 signaling upregulates both of these cytokines. Higher level of MMP-2 induction by inflammatory cytokines during arthritis promotes tissue destruction...
February 2018: Immunologic Research
Julia A Lopatnikova, Alina A Alshevskaya, Olga L Krugleeva, Vera M Nepomnyschih, Victor S Gladkikh, Vitaliy L Lukinov, Alexander V Karaulov, Sergey Vitalievich Sennikov
BACKGROUND: Expression levels of cytokine and growth factor receptors have been found to be important in the regulation of their action. Tumor necrosis factor-α (TNFα) is actively involved in inflammation processes in atopic dermatitis (AD), but the role of TNFα membrane receptors (TNFR) and their regulatory function in AD remains unclear. AIM: We aimed to determine the associations of parameters of TNFRα expression on immunocompetent cells with disease severity before and after therapy in AD patients...
2017: International Archives of Allergy and Immunology
Zijuan Zhou, Liang Wang, Panpan Feng, Lianhong Yin, Chen Wang, Shengxu Zhi, Jianyi Dong, Jingyu Wang, Yuan Lin, Dapeng Chen, Yongjian Xiong, Jinyong Peng
Activation of the TNF-α receptor (TNFR) leads to an inflammatory response, and anti-TNF therapy has been administered to reduce inflammation symptoms and heal mucosal ulcers in inflammatory bowel disease (IBD). Bromelain, a complex natural mixture of proteolytic enzymes, has been shown to exert anti-inflammatory effects. This study aimed to investigate the effect of purified fruit bromelain (PFB)-induced inhibition of epithelial TNFR in a rat colitis model. Colitis was established by intracolonic administration of 2, 4, 6-trinitrobenzene sulfonic acid...
2017: Frontiers in Immunology
Yicheng Qi, Yulin Zhou, Xinxin Chen, Lei Ye, Qianwei Zhang, Fengjiao Huang, Bin Cui, Dongping Lin, Guang Ning, Weiqing Wang, Shu Wang
Context: Aberrant CD4+ T cell function plays a critical role in the process of Graves' disease (GD). MicroRNAs (miRNAs) are important regulators of T cell activation, proliferation, and cytokine production. However, the contribution of miRNAs to CD4+ T cell dysfunction in GD remains unclear. Objective: To investigate how certain miRNA causes aberrant CD4+ T cell function in GD patients. Methods: We compared the expression pattern of miRNAs in CD4+ T cells from untreated GD (UGD) patients with those from healthy controls...
2017: Frontiers in Immunology
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