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https://www.readbyqxmd.com/read/29339199/neutralization-of-tnfr-1-and-tnfr-2-modulates-s-aureus-induced-septic-arthritis-by-regulating-the-levels-of-pro-inflammatory-and-anti-inflammatory-cytokines-during-the-progression-of-the-disease
#1
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
https://www.readbyqxmd.com/read/29305435/an-immunotherapeutic-cd137-agonist-releases-eomesodermin-from-thpok-repression-in-cd4-t-cells
#2
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
https://www.readbyqxmd.com/read/29258611/progranulin-derivative-atsttrin-protects-against-early-osteoarthritis-in-mouse-and-rat-models
#3
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
https://www.readbyqxmd.com/read/29242193/crystal-structure-of-murine-4-1bb-and-its-interaction-with-4-1bbl-support-a-role-for-galectin-9-in-4-1bb-signaling
#4
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
https://www.readbyqxmd.com/read/29233615/diet-quality-inflammation-and-quality-of-life-in-breast-cancer-survivors-a-cross-sectional-analysis-of-pilot-study-data
#5
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
https://www.readbyqxmd.com/read/29228978/asiatic-acid-attenuates-methamphetamine-induced-neuroinflammation-and-neurotoxicity-through-blocking-of-nf-kb-stat3-erk-and-mitochondria-mediated-apoptosis-pathway
#6
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
https://www.readbyqxmd.com/read/29218573/dual-neutralization-of-tnfr-2-and-mmp-2-regulates-the-severity-of-s-aureus-induced-septic-arthritis-correlating-alteration-in-the-level-of-interferon-gamma-and-interleukin-10-in-terms-of-tnfr2-blocking
#7
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...
December 7, 2017: Immunologic Research
https://www.readbyqxmd.com/read/29212072/expression-of-tnf%C3%AE-receptors-on-immunocompetent-cells-is-increased-in-atopic-dermatitis
#8
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
https://www.readbyqxmd.com/read/29176974/inhibition-of-epithelial-tnf-%C3%AE-receptors-by-purified-fruit-bromelain-ameliorates-intestinal-inflammation-and-barrier-dysfunction-in-colitis
#9
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
https://www.readbyqxmd.com/read/29163513/microrna-4443-causes-cd4-t-cells-dysfunction-by-targeting-tnfr-associated-factor-4-in-graves-disease
#10
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
https://www.readbyqxmd.com/read/29162452/dt-13-ameliorates-tnf-%C3%AE-induced-nitric-oxide-production-in-the-endothelium-in-vivo-and-in-vitro
#11
Ruiping Fan, Yuwei Han, Han Han, Zhengdong Chen, Boyang Yu, Junping Kou, Yuanyuan Zhang
The steroidal saponin DT-13 (25(R,S)-ruscogenin-1-O-[β-d-glucopyranosyl-(1 → 2)][β-d-xylopyranosyl-(1 → 3)]-β-d-fucopyranoside), one of the major active compounds of the herb Liriope muscari (Decne.), exhibits significant anti-inflammatory, anti-tumour and cardioprotective effects. This study aimed to explore the protective effect of DT-13 on endothelium through regulating of nitric oxide production induced by TNF-α. The results demonstrated that DT-13 inhibits inflammatory cell infiltration and thus plays a protective effect, as shown by H&E staining and immunohistochemical staining...
November 18, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29152082/panbinostat-decreases-cflip-and-enhances-killing-of-cancer-cells-by-immunotoxin-lmb-100-by-stimulating-the-extrinsic-apoptotic-pathway
#12
Xiu-Fen Liu, Qi Zhou, Raffit Hassan, Ira Pastan
LMB-100 (RG7787) is a recombinant immunotoxin, which kills mesothelin-expressing cancer cells and now being evaluated in phase 1 trials. To enhance the anti-tumor activity of LMB-100, we have searched for agents, already approved for cancer therapy, that can be combined with LMB-100 to increase its efficacy. Panbinostat is a pan-histone deacetylase inhibitor that is used to treat multiple myeloma. We incubated different types of cancer cells with panbinostat and LMB-100 and found that they interacted synergistically to cause cell death...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29109283/sirp%C3%AE-dendritic-cells-regulate-homeostasis-of-fibroblastic-reticular-cells-via-tnf-receptor-ligands-in-the-adult-spleen
#13
Yasuyuki Saito, Datu Respatika, Satomi Komori, Ken Washio, Taichi Nishimura, Takenori Kotani, Yoji Murata, Hideki Okazawa, Hiroshi Ohnishi, Yoriaki Kaneko, Katsuyuki Yui, Koji Yasutomo, Chikako Nishigori, Yoshihisa Nojima, Takashi Matozaki
In secondary lymphoid organs, development and homeostasis of stromal cells such as podoplanin (Pdpn)-positive fibroblastic reticular cells (FRCs) are regulated by hematopoietic cells, but the cellular and molecular mechanisms of such regulation have remained unclear. Here we show that ablation of either signal regulatory protein α (SIRPα), an Ig superfamily protein, or its ligand CD47 in conventional dendritic cells (cDCs) markedly reduced the number of CD4(+) cDCs as well as that of Pdpn(+) FRCs and T cells in the adult mouse spleen...
November 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29109120/cd27-mediated-regulatory-t-cell-depletion-and-effector-t-cell-costimulation-both-contribute-to-antitumor-efficacy
#14
Anna Wasiuk, James Testa, Jeff Weidlick, Crystal Sisson, Laura Vitale, Jenifer Widger, Andrea Crocker, Lawrence J Thomas, Joel Goldstein, Henry C Marsh, Tibor Keler, Li-Zhen He
CD27, a member of the TNFR superfamily, is constitutively expressed in most T cells and plays crucial roles in T cell effector functions. The costimulation and antitumor activity of CD27 agonistic Abs have been well documented in mouse models. Clinical testing of a human IgG1 anti-CD27 Ab, varlilumab (clone 1F5), is ongoing in cancer patients. In this study, we set out to further understand CD27 as an immunomodulatory target and to address the mechanism of antitumor efficacy using different IgG isotypes of 1F5 in human CD27-transgenic mice...
November 6, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29108854/socs-1-ameliorates-smoke-inhalation-induced-acute-lung-injury-through-inhibition-of-ask-1-activity-and-disc-formation
#15
Leifang Zhang, Kairei Zhu, Yating Ma, Chenming Xu, Qiwen Shi, Xiaoming Chen, Weike Su, Hang Zhao
Smoke inhalation leads to acute lung injury (ALI), a devastating clinical problem associated with high mortality. Suppressor of cytokine signaling-1 (SOCS-1) is a negative regulator of apoptosis and pro-inflammatory cytokine signaling, two major contributors to the pathogenesis of ALI. We have found that SOCS-1 protects lung epithelial cells from smoke-induced apoptosis through two mechanisms. One is that SOCS-1 enhances degradation of ASK-1 and diminishes cleavage of pro-caspase-3 to repress smoke-triggered apoptosis in lung epithelial cells...
November 3, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/29066276/signaling-by-cell-surface-death-receptors-alterations-in-head-and-neck-cancer
#16
REVIEW
Brandon C Leonard, Daniel E Johnson
Cell surface death receptors are members of the tumor necrosis factor receptor (TNFR) superfamily and mediate signals leading to the induction of apoptosis or necroptosis, as well as NF-κB-mediated cell survival. These biochemical processes play key roles in cell growth, development, tissue homeostasis, and immune responses. The downstream signaling complexes activated by different death receptors can differ significantly and are subject to multiple, distinct regulatory mechanisms. Dysregulation of signaling by the TNFR superfamily contributes to a variety of pathologic conditions, including defective immune responses and cancer...
October 18, 2017: Advances in Biological Regulation
https://www.readbyqxmd.com/read/29062811/activation-of-nf-kb-mediated-tnf-induced-antimicrobial-immunity-is-required-for-the-efficient-brucella-abortus-clearance-in-raw-264-7-cells
#17
Huynh T Hop, Alisha W B Reyes, Tran X N Huy, Lauren T Arayan, WonGi Min, Hu J Lee, Man H Rhee, Hong H Chang, Suk Kim
In this study, we explore the regulatory roles of pro-inflammatory cytokine tumor necrosis factor alpha (TNF) in the innate immunity of macrophages against B. abortus infection. We show that infection of macrophage with B. abortus induces marked expression and secretion of TNF which subsequently binds to TNF receptor 1 (TNFR-1) and activates a downstream signaling cascade of the innate immunity. Blocking of TNF signaling resulted in a notable increase of B. abortus survival which was associated with an increase of anti-inflammatory cytokine interleukin 10 (IL-10), a beneficial effector of Brucella survival, as well as remarkable decrease of reactive oxygen species (ROS) and nitric oxide (NO), antibrucella molecules...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/29052145/cell-death-pathways-a-novel-therapeutic-approach-for-neuroscientists
#18
REVIEW
G Morris, A J Walker, M Berk, M Maes, B K Puri
In the first part, the following mechanisms involved in different forms of cell death are considered, with a view to identifying potential therapeutic targets: tumour necrosis factor receptors (TNFRs) and their engagement by tumour necrosis factor-alpha (TNF-α); poly [ADP-ribose] polymerase (PARP)-1 cleavage; the apoptosis signalling kinase (ASK)-c-Jun N-terminal kinase (JNK) axis; lysosomal permeability; activation of programmed necrotic cell death; oxidative stress, caspase-3 inhibition and parthanatos; activation of inflammasomes by reactive oxygen species and the development of pyroptosis; oxidative stress, calcium dyshomeostasis and iron in the development of lysosomal-mediated necrosis and lysosomal membrane permeability; and oxidative stress, lipid peroxidation, iron dyshomeostasis and ferroptosis...
October 19, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/29038485/a-versatile-pretargeting-approach-for-tumour-selective-delivery-and-activation-of-tnf-superfamily-members
#19
Yuan He, Peter E van Bommel, Douwe F Samplonius, Edwin Bremer, Wijnand Helfrich
TNFR superfamily (TNFRSF) members have important immunoregulatory functions and are of clear interest for cancer immunotherapy. Various TNFRSF agonists have been clinically evaluated, but have met with limited efficacy and/or toxicity. Recent insights indicate that 'first-generation' TNFRSF agonists lack efficacy as they do not effectively cross-link their corresponding receptor. Reversely, ubiquitous TNFRSF receptor(s) cross-linking by CD40 and Fas agonistic antibodies resulted in dose-limiting liver toxicity...
October 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29038250/inhibition-of-irak1-ubiquitination-determines-glucocorticoid-sensitivity-for-tlr9-induced-inflammation-in-macrophages
#20
Fansheng Kong, Zhiwei Liu, Viral G Jain, Kenjiro Shima, Takuji Suzuki, Louis J Muglia, Daniel T Starczynowski, Chandrashekhar Pasare, Sandip Bhattacharyya
Inflammatory responses are controlled by signaling mediators that are regulated by various posttranslational modifications. Recently, transcription-independent functions for glucocorticoids (GC) in restraining inflammation have emerged, but the underlying mechanisms are unknown. In this study, we report that GC receptor (GR)-mediated actions of GC acutely suppress TLR9-induced inflammation via inhibition of IL-1R-associated kinase 1 (IRAK1) ubiquitination. β-TrCP-IRAK1 interaction is required for K48-linked ubiquitination of IRAK1 at Lys(134) and subsequent membrane-to-cytoplasm trafficking of IRAK1 interacting partners TNFR-associated factor 6 and TAK1 that facilitates NF-κB and MAPK activation...
November 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
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