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https://www.readbyqxmd.com/read/28446565/murinization-and-h-chain-isotype-matching-of-the-anti-gitr-antibody-dta-1-reduces-immunogenicity-mediated-anaphylaxis-in-c57bl-6-mice
#1
Nicole A Belmar, Sarah W Chan, Melvin I Fox, Josue A Samayoa, Marcia M Stickler, Ninian N Tran, Yoshiko Akamatsu, Diane Hollenbaugh, Fiona A Harding, Hamsell M Alvarez
Recent advances in immuno-oncology have shown that the immune system can be activated to induce long-term, durable antitumor responses. For immuno-oncology drug development, immune activation is often explored using rat Abs in immunocompetent mouse models. Although these models can be used to show efficacy, antidrug immune responses to experimental protein-based therapeutics can arise. Immunogenicity of surrogate Abs may therefore represent an important obstacle to the evaluation of the antitumor efficacy of immunomodulator Abs in syngeneic models...
April 26, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28420753/the-kinase-tpl2-activates-erk-and-p38-signaling-to-promote-neutrophilic-inflammation
#2
Kate Senger, Victoria C Pham, Eugene Varfolomeev, Jason A Hackney, Cesar A Corzo, Jenna Collier, Vivian W C Lau, Zhiyu Huang, Kajal Hamidzhadeh, Patrick Caplazi, Ivan Peng, A Francesca Setiadi, Ross Francis, Andres Paler-Martinez, Youngsu C Kwon, Vladimir Ramirez-Carrozzi, Yonglian Sun, Patricia W Grigg, Merone Roose-Girma, Surinder Jeet, Kai H Barck, Anna Pham, Naruhisa Ota, Connie Ha, Jeremy Stinson, Joseph Guillory, Lucinda Tam, Zora Modrusan, Claire Emson, Brent S McKenzie, Michael J Townsend, Richard A D Carano, Søren Warming, Domagoj Vucic, Jason DeVoss, Wyne P Lee, Jennie R Lill, Ali A Zarrin
Tumor progression locus 2 (TPL2; also known as MAP3K8) is a mitogen-activated protein kinase (MAPK) kinase kinase (MAP3K) that phosphorylates the MAPK kinases MEK1 and MEK2 (MEK1/2), which, in turn, activate the MAPKs extracellular signal-regulated kinase 1 (ERK1) and ERK2 (ERK1/2) in macrophages stimulated through the interleukin-1 receptor (IL-1R), Toll-like receptors (TLRs), or the tumor necrosis factor receptor (TNFR). We describe a conserved and critical role for TPL2 in mediating the effector functions of neutrophils through the activation of the p38 MAPK signaling pathway...
April 18, 2017: Science Signaling
https://www.readbyqxmd.com/read/28418397/bap180-baf180-is-required-to-maintain-homeostasis-of-intestinal-innate-immune-response-in-drosophila-and-mice
#3
Xiaomeng He, Junjing Yu, Min Wang, Yang Cheng, Yanan Han, Shuo Yang, Guizhi Shi, Lei Sun, Ying Fang, Si-Tang Gong, Zhong Wang, Yang-Xin Fu, Lei Pan, Hong Tang
Immune homeostasis is a prerequisite to protective immunity against gastrointestinal infections. In Drosophila, immune deficiency (IMD) signalling (tumour necrosis factor receptor/interleukin-1 receptor, TNFR/IL-1R in mammals) is indispensable for intestinal immunity against invading bacteria. However, how this local antimicrobial immune response contributes to inflammatory regulation remains poorly defined. Here, we show that flies lacking intestinal Bap180 (a subunit of the chromatin-remodelling switch/sucrose non-fermentable (SWI/SNF) complex) are susceptible to infection as a result of hyper-inflammation rather than bacterial overload...
April 18, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/28412413/activation-of-muscarinic-receptors-prevents-tnf-%C3%AE-mediated-intestinal-epithelial-barrier-disruption-through-p38-mapk
#4
Junsuke Uwada, Takashi Yazawa, Md Tariqul Islam, Md Rafiqul Islam Khan, Susanne M Krug, Michael Fromm, Shin-Ichiro Karaki, Yuichi Suzuki, Atsukazu Kuwahara, Hatsumi Yoshiki, Kiyonao Sada, Ikunobu Muramatsu, Takanobu Taniguchi
Intestinal epithelial cells form a tight barrier to act as selective physical barriers, repelling hostile substances. Tumor necrosis factor-α (TNF-α) is a well characterized pro-inflammatory cytokine which can compromise intestinal barrier function and the suppression of TNF-α function is important for treatment of inflammatory bowel disease (IBD). In this study, we investigated the contribution of G-protein-coupled receptor (GPCR)-induced signalling pathways to the maintenance of epithelial barrier function...
April 12, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28411279/characterization-and-interspecies-scaling-of-rhtnf-%C3%AE-pharmacokinetics-with-minimal-physiologically-based-pharmacokinetic-mpbpk-models
#5
Xi Chen, Debra C DuBois, Richard R Almon, William J Jusko
Tumor necrosis factor-α (TNF-α) is a soluble cytokine and target of specific monoclonal antibodies (mAbs) and other biological agents used for the treatment of inflammatory diseases. These biologics exert their pharmacological effects through binding and neutralizing TNF-α, and thus prevent TNF-α from interacting with its cell surface receptors. The magnitude of pharmacological effects is governed not only by the pharmacokinetics of mAbs, but also the kinetic fate of TNF-α. We have examined the pharmacokinetics of rhTNF-α in rats at low doses and quantitatively characterized its pharmacokinetic features with a minimal physiologically-based pharmacokinetic (mPBPK) model...
April 14, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28405520/the-immune-molecular-landscape-of-the-b7-and-tnfr-immunoregulatory-ligand-receptor-families-in-head-and-neck-cancer-a-comprehensive-overview-and-the-immunotherapeutic-implications
#6
Yu-Pei Chen, Jian Zhang, Ya-Qin Wang, Na Liu, Qing-Mei He, Xiao-Jing Yang, Ying Sun, Jun Ma
The B7 family and tumor necrosis factor receptor (TNFR) superfamily play a vital role in the T-cell co-stimulatory and co-inhibitory pathways, regulating T-cell activation, tolerance, and exhaustion; therapeutic modulation of these pathways is translated into effective new cancer treatments. Better understanding of the immune molecular landscapes of the B7 and TNFR families would guide head and neck immuno-oncology clinical research. We performed comprehensive molecular profiling of 10 B7 and 6 TNFR family members in head and neck cancer...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28392436/an-oral-administration-of-a-recombinant-anti-tnf-fusion-protein-is-biologically-active-in-the-gut-promoting-regulatory-t-cells-results-of-a-phase-i-clinical-trial-using-a-novel-oral-anti-tnf-alpha-based-therapy
#7
Einat Almon, Tawfik Khoury, Ariel Drori, Svetlana Gingis-Velitski, Sari Alon, Raul Chertkoff, Mordechai Mushkat, Yoseph Shaaltiel, Yaron Ilan
BACKGROUND: An orally administered BY-2 plant cell-expressed recombinant anti-TNF fusion protein (PRX-106) consists of the soluble form of the human TNF receptor (TNFR) fused to the Fc component of a human IgG1 domain. Aim This study aim at determining the safety and the immune modulatory effect of an oral administration of PRX-106 in humans. METHODS: Three different doses (2, 8 or 16mg/day) of PRX-106 were orally administered for five consecutive days in 14 healthy volunteered participants...
April 7, 2017: Journal of Immunological Methods
https://www.readbyqxmd.com/read/28389814/effect-of-tonsillectomy-with-steroid-pulse-therapy-on-circulating-tumor-necrosis-factor-receptors-1-and-2-in-iga-nephropathy
#8
Maki Murakoshi, Tomohito Gohda, Yuji Sonoda, Hitoshi Suzuki, Yasuhiko Tomino, Satoshi Horikoshi, Yusuke Suzuki
BACKGROUND: High circulating levels of soluble tumor necrosis factor receptors (TNFRs: TNFR1, TNFR2) predict renal function decline in a variety of kidney diseases. Tonsillectomy with steroid pulse (TSP) therapy has been reported as a remission induction therapy in IgA nephropathy (IgAN), mainly in Japan. However, little is known about whether TNFR levels change after TSP therapy in patients with IgAN. METHODS: Two hundred twenty-three patients with IgAN were stratified according to the estimated glomerular filtration rate (eGFR): Group I (eGFR ≥ 60 mL/min/1...
April 7, 2017: Clinical and Experimental Nephrology
https://www.readbyqxmd.com/read/28367848/tnf-receptor-1-2-predict-heart-failure-risk-in-type-2-diabetes-mellitus-patients
#9
Zhang Ping, Ma Aiqun, Li Jiwu, Shao Liang
Inflammation plays an important role in heart failure and diabetes mellitus. Traditional serum markers have limited predictive value in heart failure and diabetes. TNFR1 and TNFR2 (TNFR1/2) have been proven to be strongly associated with heart failure and diabetes complications. This study aimed to assess the association of sTNFR1 and sTNFR2 levels and incidental HF risk in diabetes patients.We detected the mRNA, protein, and serum expression of TNFR1/2, their downstream signaling pathway protein NF-kB, and JNK expression and some traditional serum inflammatory markers in a heart failure group without diabetes mellitus or abnormal glucose tolerance (n = 84), a diabetes mellitus group without heart failure (n = 86), and a heart failure with diabetes mellitus group (n = 86)...
April 6, 2017: International Heart Journal
https://www.readbyqxmd.com/read/28365939/high-expression-of-herpesvirus-entry-mediator-hvem-in-ovarian-serous-adenocarcinoma-tissue
#10
Yuan Fang, Lei Ye, Ting Zhang, Qi-Zhi He, Jian-Long Zhu
PURPOSE: To explore the expression of herpesvirus entry mediator (HVEM) in ovarian serous adenocarcinoma tissues and its relationship with clinicopathological features. METHODS: Paraffin-embedded specimens from 40 patients with ovarian serous adenocarcinoma who were subjected to surgical treatment were used for the determination of HVEM expression by immunohistochemistry (IHC). Then the relationship between the expression of HVEM and the patient clinicopathological features was analyzed...
January 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/28358311/targeting-tnf-and-tnf-receptor-pathway-in-hiv-1-infection-from-immune-activation-to-viral-reservoirs
#11
REVIEW
Sébastien Pasquereau, Amit Kumar, Georges Herbein
Several cellular functions such as apoptosis, cellular proliferation, inflammation, and immune regulation involve the tumor necrosis factor-α (TNF)/TNF receptor (TNFR) pathway. Human immunodeficiency virus 1 (HIV-1) interacts with the TNF/TNFR pathway. The activation of the TNF/TNFR pathway impacts HIV-1 replication, and the TNF/TNFR pathway is the target of HIV-1 proteins. A hallmark of HIV-1 infection is immune activation and inflammation with increased levels of TNF in the plasma and the tissues. Therefore, the control of the TNF/TNFR pathway by new therapeutic approaches could participate in the control of immune activation and impact both viral replication and viral persistence...
March 30, 2017: Viruses
https://www.readbyqxmd.com/read/28315393/tumor-necrosis-factor-receptor-associated-factor-6-traf6-participates-in-peroxinectin-gene-expression-in-fenneropenaeus-penicillatus
#12
Shuanghu Cai, Yucong Huang, Bei Wang, Jichang Jian, Youhou Xu
Tumor necrosis factor receptor-associated factor 6 (TRAF6) is an important cytoplasm signal adaptor that mediates signals activated by tumor necrosis factor receptor (TNFR) superfamily and the Interleukin-1 receptor/Toll-like receptor (IL-1/TLR) superfamily. In the study, the full-length cDNA of a TRAF6 homolog (FpTRAF6) was identified from Fenneropenaeus penicillatus. The full-length cDNA of FpTRAF6 is 2033 bp long, with an open reading frame (ORF) encoding a putative protein of 594 amino acids, including a RING type Zinc finger, two TRAF-type Zinc fingers, and a conserved C-terminal meprin and TRAF homology (MATH) domain...
May 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28300056/imbalance-between-tnf%C3%AE-and-progranulin-contributes-to-memory-impairment-and-anxiety-in-sleep-deprived-mice
#13
Kun Zhang, Yu-Jiao Li, Dan Feng, Peng Zhang, Ya-Tao Wang, Xiang Li, Shui-Bing Liu, Yu-Mei Wu, Ming-Gao Zhao
Sleep disorder is becoming a widespread problem in current society, and is associated with impaired cognition and emotional disorders. Progranulin (PGRN), also known as granulin epithelin precursor, promotes neurite outgrowth and cell survival, and is encoded by the GRN gene. It is a tumor necrosis factor α receptor (TNFR) ligand which is implicated in many central nervous system diseases. However, the role PGRN in sleep disorder remains unclear. In the present study, we found that sleep deprivation (S-DEP) impaired the memory and produced thigmotaxis/anxiety-like behaviors in mice...
March 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28289704/preferential-tnf%C3%AE-signaling-via-tnfr2-regulates-epithelial-injury-and-duct-obstruction-in-experimental-biliary-atresia
#14
Pranavkumar Shivakumar, Tatsuki Mizuochi, Reena Mourya, Sridevi Gutta, Li Yang, Zhenhua Luo, Jorge A Bezerra
Biliary atresia is an obstructive cholangiopathy of infancy that progresses to end-stage cirrhosis. Although the pathogenesis of the disease is not completely understood, previous reports link TNFα to apoptosis of the bile duct epithelium in the presence of IFNγ. Here, we investigate if TNFα signaling regulates pathogenic mechanisms of biliary atresia. First, we quantified the expression of TNFA and its receptors TNFR1 and TNFR2 in human livers and found an increased expression of the receptors at the time of diagnosis...
March 9, 2017: JCI Insight
https://www.readbyqxmd.com/read/28256549/circulating-tnf-receptors-1-and-2-predict-mortality-in-patients-with-end-stage-renal-disease-undergoing-dialysis
#15
Tomohito Gohda, Shuntaro Maruyama, Nozomu Kamei, Saori Yamaguchi, Terumi Shibata, Maki Murakoshi, Satoshi Horikoshi, Yasuhiko Tomino, Isao Ohsawa, Hiromichi Gotoh, Shuko Nojiri, Yusuke Suzuki
Relatively high circulating levels of soluble tumor necrosis factor (TNF) receptors (TNFRs: TNFR1, TNFR2) have been associated with not only progression to end-stage renal disease but also mortality in patients with diabetes. It remains unknown whether elevated TNFR levels in haemodialysis patients are associated with mortality. We studied 319 patients receiving maintenance haemodialysis who were followed for a median of 53 months. Circulating markers of TNF pathway (TNFα and TNFRs) were measured with immunoassay...
March 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28250156/microrna-3570-modulates-the-nf-%C3%AE%C2%BAb-pathway-in-teleost-fish-by-targeting-myd88
#16
Qing Chu, Yuena Sun, Junxia Cui, Tianjun Xu
The inflammatory response, a protective process to clear detrimental stimuli, constitutes the defense against infectious pathogens. However, excessive inflammation disrupts immune homeostasis, which may induce autoimmune and inflammatory diseases. In this study, we report that microRNA (miR)-3570 plays a negative role in the bacteria-induced inflammatory response of miiuy croaker. Upregulation of miR-3570 by Vibrio anguillarum and LPS inhibits LPS-induced inflammatory cytokine production, thus avoiding an excessive inflammation response...
March 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28229280/posterior-urethral-valve-in-fetuses-evidence-for-the-role-of-inflammatory-molecules
#17
Érica Leandro Marciano Vieira, Natalia Pessoa Rocha, Fernando Macedo Bastos, Kátia Daniela da Silveira, Alamanda K Pereira, Eduardo Araújo Oliveira, Débora Marques de Miranda, Ana Cristina Simões E Silva
BACKGROUND: The aim of this cross-sectional study was to investigate inflammatory biomarkers in urine samples of 24 fetuses with posterior urethral valve (PUV) collected at 22 ± 4 weeks of gestation and to compare the findings with measurements in urine samples of 22 male healthy preterm neonates at 23 ± 4 weeks (control group). METHODS: Inflammatory biomarkers in urine were measured using a cytometric bead array [interleukin (IL)-2, IL-4, IL-6, IL-10, interferon (IFN)-γ, soluable tumor necrosis factor receptor (TNFR) 1, sTNFR2, monocyte chemoattractant protein-1/chemokine ligand 2 (MCP-1/CCL2), eotaxin/CCL11 and interferon gamma-induced protein/10/C-X-C motif chemokine 10 (IP-10/CXCL10)] and ELISA assays [TNF, IL-8/CXCL8 and transforming growth factor-beta (TGF-β)]...
February 22, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28215307/structural-characterization-of-the-p75-neurotrophin-receptor-a-stranger-in-the-tnfr-superfamily
#18
M Vilar
Although p75 neurotrophin receptor (p75(NTR)) was the founding member of the tumor necrosis factor (TNF) receptor superfamily (TNFRSF), it is an atypical TNFRSF protein. p75(NTR) like TNF-R1 and Fas-R contain an extracellular domain with four cysteine-rich domains (CRD) and a death domain (DD) in the intracellular region. While TNFRSF proteins are activated by trimeric TNFSF ligands, p75(NTR) forms dimers activated by dimeric neurotrophins that are structurally unrelated to TNFSF proteins. In addition, although p75(NTR) shares with other members the interaction with the TNF receptor-associated factors to activate the NF-κB and cell death pathways, p75(NTR) does not interact with the DD-containing proteins FADD, TRADD, or MyD88...
2017: Vitamins and Hormones
https://www.readbyqxmd.com/read/28211786/sieving-and-extraction-of-peptides-and-proteins-during-hemofiltration-a-systematic-review%C3%A2
#19
J Scott Baird
The relationship between the sieving coefficient (SC) or extraction ratio (ER) and the molecular weight (MW) of peptide and protein solutes during hemofiltration has not been investigated; it is possible that the SC and ER correlate with MW, permitting an estimate of peptide and protein clearance by hemofiltration in the absence of empiric data. A search for studies of the SC and/or ER for peptide and protein solutes during hemofiltration identified data for β2-microglobulin, brain natriuretic peptide, carperitide, IL-1β, IL-1RA, IL-6, IL-8, lysozyme, myoglobin, neutrophil gelatinase-associated lipocalin, procalcitonin, retinol-binding protein, TNF-α, soluble TNFR-1, soluble TNFR-II, and vasopressin using polyacrylonitrile, polysulfone, polyamide, and cellulose hemofilters...
February 17, 2017: Clinical Nephrology
https://www.readbyqxmd.com/read/28159803/tripartite-motif-containing-28-bridges-endothelial-inflammation-and-angiogenic-activity-by-retaining-expression-of-tnfr-1-and-2-and-vegfr2-in-endothelial-cells
#20
Yinfang Wang, Jinping Li, Yitong Huang, Xiuqin Dai, Youbin Liu, Zongjun Liu, Ying Wang, Nanping Wang, Peng Zhang
Angiogenesis and inflammation are regarded as important factors in the pathogenesis of chronic inflammation, cancer, and wound healing. Recent studies have supported prior evidence that common signaling pathways are involved in angiogenesis and inflammatory responses; however, key factors controlling both processes remain unclear. Although tripartite motif-containing (TRIM)-28 is known to have an immunosuppressive role in immune cells, its expression level and role in endothelial cells (ECs) are still unclear...
February 3, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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