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https://www.readbyqxmd.com/read/29297499/differential-regulation-of-the-transcriptomic-and-secretomic-landscape-of-sensor-and-effector-functions-of-human-airway-epithelial-cells
#1
Roland Lehmann, Mario M Müller, Tilman E Klassert, Dominik Driesch, Magdalena Stock, Anina Heinrich, Theresia Conrad, Christoph Moore, Uta K Schier, Reinhard Guthke, Hortense Slevogt
Protein secretion upon TLR, TNFR1, and IFNGR ligation in the human airways is considered to be central for the orchestration of pulmonary inflammatory and immune responses. In this study, we compared the gene expression and protein secretion profiles in response to specific stimulation of all expressed TLRs and in further comparison to TNFR1 and IFNGR in primary human airway epithelial cells. In addition to 22 cytokines, we observed the receptor-induced regulation of 571 genes and 1,012 secreted proteins. Further analysis revealed high similarities between the transcriptional TLR sensor and TNFR1 effector responses...
January 3, 2018: Mucosal Immunology
https://www.readbyqxmd.com/read/29273790/tnf%C3%AE-blockade-overcomes-resistance-to-anti-pd-1-in-experimental-melanoma
#2
Florie Bertrand, Anne Montfort, Elie Marcheteau, Caroline Imbert, Julia Gilhodes, Thomas Filleron, Philippe Rochaix, Nathalie Andrieu-Abadie, Thierry Levade, Nicolas Meyer, Céline Colacios, Bruno Ségui
Antibodies against programmed cell death-1 (PD-1) have considerably changed the treatment for melanoma. However, many patients do not display therapeutic response or eventually relapse. Moreover, patients treated with anti-PD-1 develop immune-related adverse events that can be cured with anti-tumor necrosis factor α (TNF) antibodies. Whether anti-TNF antibodies affect the anti-cancer immune response remains unknown. Our recent work has highlighted that TNFR1-dependent TNF signalling impairs the accumulation of CD8+ tumor-infiltrating T lymphocytes (CD8+ TILs) in mouse melanoma...
December 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/29273047/donepezil-suppresses-intracellular-ca2-mobilization-through-the-pi3k-pathway-in-rodent-microglia
#3
Yoshinori Haraguchi, Yoshito Mizoguchi, Masahiro Ohgidani, Yoshiomi Imamura, Toru Murakawa-Hirachi, Hiromi Nabeta, Hiroshi Tateishi, Takahiro A Kato, Akira Monji
BACKGROUND: Microglia are resident innate immune cells which release many factors including proinflammatory cytokines or nitric oxide (NO) when they are activated in response to immunological stimuli. Pathophysiology of Alzheimer's disease (AD) is related to the inflammatory responses mediated by microglia. Intracellular Ca2+ signaling is important for microglial functions such as release of NO and cytokines. In addition, alteration of intracellular Ca2+ signaling underlies the pathophysiology of AD, while it remains unclear how donepezil, an acetylcholinesterase inhibitor, affects intracellular Ca2+ mobilization in microglial cells...
December 22, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29258611/progranulin-derivative-atsttrin-protects-against-early-osteoarthritis-in-mouse-and-rat-models
#4
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/29246259/macrophages-in-trigeminal-ganglion-contribute-to-ectopic-mechanical-hypersensitivity-following-inferior-alveolar-nerve-injury-in-rats
#5
Dulguun Batbold, Masamichi Shinoda, Kuniya Honda, Akihiko Furukawa, Momoko Koizumi, Ryuta Akasaka, Satoshi Yamaguchi, Koichi Iwata
BACKGROUND: Accidental mandibular nerve injury may occur during tooth extraction or implant procedures, causing ectopic orofacial pain. The exact mechanisms underlying ectopic orofacial pain following mandibular nerve injury is still unknown. Here, we investigated the role of macrophages and tumor necrosis factor alpha (TNFα) in the trigeminal ganglion (TG) in ectopic orofacial pain following inferior alveolar nerve transection (IANX). METHODS: IANX was performed and the mechanical head-withdrawal threshold (MHWT) in the whisker pad skin ipsilateral to IANX was measured for 15 days...
December 16, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29243062/pre-clinical-study-of-a-tnfr1-targeted-18f-probe-for-pet-imaging-of-breast-cancer
#6
Hao Fu, Hua Wu, Xianzhong Zhang, Jinxiong Huang, Xiaojiang He, Lichun Chen, Wei Guo, Xiuyu Guo, Bing Hao, Yesen Li
Tumor necrosis factor receptor 1 (TNFR1) is overexpressed in several varieties of carcinoma, including breast cancer. WH701 (Ala-Thr-Ala-Gln-Ser-Ala-Tyr-Gly), which was identified by phage display, can specifically bind to TNFR1. In this study, we labeled WH701 with 18F and investigated its tumor diagnostic value. WH701 was synthesized by standard Fmoc-solid phase synthetic protocols and conjugated by NOTA-NHS. NOTA-WH701 was radiolabeled with 18F using NOTA-AlF chelation reaction. The tumor target properties were evaluated in vitro and in vivo using MCF-7 xenografts and inflammation models...
December 14, 2017: Amino Acids
https://www.readbyqxmd.com/read/29234328/forward-and-reverse-signaling-mediated-by-transmembrane-tumor-necrosis-factor-alpha-and-tnf-receptor-2-potential-roles-in-an-immunosuppressive-tumor-microenvironment
#7
REVIEW
Yang Qu, Gang Zhao, Hui Li
Tumor necrosis factor-alpha (TNF-α) is a pleiotropic inflammatory cytokine produced mainly by activated macrophages, lymphocytes and other cell types. Two distinct forms of TNF-α have been identified: soluble TNF-α (sTNF-α) and transmembrane TNF-α (mTNF-α). mTNF-α, which is the precursor of sTNF-α, can be cleaved by the TNF-α converting enzyme (TACE) and is released as sTNF-α. sTNF-α binds primarily to TNF receptor 1 (TNFR1) and plays an important role in the inflammatory immune response, whereas mTNF-α interacts primarily with TNF receptor 2 (TNFR2) and mediates the promotion of cellular proliferation and survival and other biological effects...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29233887/st6gal-i-sialyltransferase-promotes-tumor-necrosis-factor-tnf-mediated-cancer-cell-survival-via-sialylation-of-the-tnf-receptor-1-tnfr1-death-receptor
#8
Andrew T Holdbrooks, Colleen M Britain, Susan L Bellis
Activation of the TNFR1 death receptor by TNF induces either cell survival or cell death. However, the mechanisms mediating these distinct outcomes remain poorly understood. In the present study, we report that the ST6Gal-I sialyltransferase, an enzyme upregulated in numerous cancers, sialylates TNFR1, and thereby protects tumor cells from TNF-induced apoptosis. Using pancreatic and ovarian cancer cells with ST6Gal-I knockdown or overexpression, we determined that α2-6 sialylation of TNFR1 had no effect on early TNF-induced signaling events including the rapid activation of NFκB, JNK, ERK, and Akt (occurring within 15m)...
December 12, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29229989/necroptotic-signaling-is-primed-in-mycobacterium-tuberculosis-infected-macrophages-but-its-pathophysiological-consequence-in-disease-is-restricted
#9
Michael D Stutz, Samar Ojaimi, Cody Allison, Simon Preston, Philip Arandjelovic, Joanne M Hildebrand, Jarrod J Sandow, Andrew I Webb, John Silke, Warren S Alexander, Marc Pellegrini
Mixed lineage kinase domain-like (MLKL)-dependent necroptosis is thought to be implicated in the death of mycobacteria-infected macrophages, reportedly allowing escape and dissemination of the microorganism. Given the consequent interest in developing inhibitors of necroptosis to treat Mycobacterium tuberculosis (Mtb) infection, we used human pharmacologic and murine genetic models to definitively establish the pathophysiological role of necroptosis in Mtb infection. We observed that Mtb infection of macrophages remodeled the intracellular signaling landscape by upregulating MLKL, TNFR1, and ZBP1, whilst downregulating cIAP1, thereby establishing a strong pro-necroptotic milieu...
December 11, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29223372/diagnostic-and-prognostic-plasma-biomarkers-for-idiopathic-pneumonia-syndrome-after-hematopoietic-cell-transplantation
#10
Sachiko Seo, Jeffrey Yu, Isaac C Jenkins, Wendy M Leisenring, Terry Steven-Ayers, Jane M Kuypers, Meei-Li Huang, Keith R Jerome, Michael Boeckh, Sophie Paczesny
Idiopathic pneumonia syndrome (IPS) is a non-infectious pulmonary complication after hematopoietic cell transplantation (HCT) and is difficult to diagnose. We evaluated six candidate proteins in plasma samples at day 7 after HCT and at onset of IPS from 41 IPS cases to identify potential IPS diagnostic or prognostic biomarkers. Samples at similar times from 162 HCT recipients without documented infections and 37 HCT recipients with respiratory viral pneumonia served as controls. In multivariable models, a combination of Stimulation-2 (ST2, OR 2...
December 6, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29215702/adam17-participates-in-the-protective-effect-of-paeoniflorin-on-mouse-brain-microvascular-endothelial-cells
#11
Haifang Wang, Shuhui Ma, Jing Li, Miaomiao Zhao, Xueping Huo, Jingying Sun, Lijun Sun, Jun Hu, Qinshe Liu
Paeoniflorin (PF), the most abundant active ingredient of traditional Chinese herbal medicine Paeoniae Radix, has been recognized as a potential neuroprotectant due to its remarkable efficacy on mitigating cerebral infarction and preventing the neurodegenerative diseases. However, the precise mechanisms of PF remain incompletely understood. In this study, we first provided evidence for the protective effect of PF on hydrogen peroxide-induced injury on mouse brain microvascular endothelial bEnd.3 cells, and for transactivation of the epidermal growth factor receptor (EGFR) signal induced by PF, suggesting that EGFR transactivation might be involved in the beneficial role of PF...
December 7, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29212072/expression-of-tnf%C3%AE-receptors-on-immunocompetent-cells-is-increased-in-atopic-dermatitis
#12
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/29203883/abin-1-regulates-ripk1-activation-by-linking-met1-ubiquitylation-with-lys63-deubiquitylation-in-tnf-rsc
#13
Slawomir A Dziedzic, Zhenyi Su, Vica Jean Barrett, Ayaz Najafov, Adnan K Mookhtiar, Palak Amin, Heling Pan, Li Sun, Hong Zhu, Averil Ma, Derek W Abbott, Junying Yuan
Ubiquitylation of the TNFR1 signalling complex (TNF-RSC) controls the activation of RIPK1, a kinase critically involved in mediating multiple TNFα-activated deleterious events. However, the molecular mechanism that coordinates different types of ubiquitylation modification to regulate the activation of RIPK1 kinase remains unclear. Here, we show that ABIN-1/NAF-1, a ubiquitin-binding protein, is recruited rapidly into TNF-RSC in a manner dependent on the Met1-ubiquitylating complex LUBAC to regulate the recruitment of A20 to control Lys63 deubiquitylation of RIPK1...
January 2018: Nature Cell Biology
https://www.readbyqxmd.com/read/29202842/preclinical-and-clinical-aspects-of-tnf-%C3%AE-and-its-receptors-tnfr1-and-tnfr2-in-breast-cancer
#14
REVIEW
Isela Martínez-Reza, Lorenza Díaz, Rocío García-Becerra
Breast cancer is the most common malignancy in women and a public health problem worldwide. Breast cancer is often accompanied by an inflammatory process characterized by the presence of proinflammatory cytokines such as tumor necrosis factor (TNF-α), which has important implications in the course of the disease. Inflammation has been described primarily as a favorable environment for tumor development. However, under certain conditions TNF-α can promote signals for activation, differentiation, survival or cell death, so the study of the variants of this cytokine, its receptors, the presence of polymorphisms and its implication in different phenotypes of breast cancer is necessary...
December 4, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/29183282/bilateral-muscle-fiber-and-nerve-influences-by-tnf-alpha-in-response-to-unilateral-muscle-overuse-studies-on-tnf-receptor-expressions
#15
Lina Renström, Per Stål, Yafeng Song, Sture Forsgren
BACKGROUND: TNF-alpha is suggested to be involved in muscle damage and muscle inflammation (myositis). In order to evaluate whether TNF-alpha is involved in the myositis that occurs in response to muscle overuse, the aim was to examine the expression patterns of TNF receptors in this condition. METHODS: A rabbit muscle overuse model leading to myositis in the soleus muscle was used. The expression patterns of the two TNF receptors Tumor Necrosis Factor Receptor type 1 (TNFR1) and Tumor Necrosis Factor Receptor type 2 (TNFR2) were investigated...
November 28, 2017: BMC Musculoskeletal Disorders
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
#16
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/29167166/blood-borne-interleukin-1%C3%AE-acts-upon-the-subfornical-organ-to-upregulate-the-sympathoexcitatory-milieu-of-the-hypothalamic-paraventricular-nucleus
#17
Shun-Guang Wei, Yang Yu, Robert B Felder
We previously reported that microinjection of the pro-inflammatory cytokine interleukin-1 beta (IL-1β) into the subfornical organ (SFO) elicits a pressor response accompanied by increases in inflammation and renin-angiotensin system (RAS) activity in the SFO and in the hypothalamic paraventricular nucleus (PVN). The present study sought to determine whether blood-borne IL-1β induces similar neurochemical changes in the SFO and PVN, and, if so, whether increased inflammation and RAS activity at the SFO level orchestrate the sympathoexcitatory response to circulating IL-1β...
November 22, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/29162483/altered-expression-of-cxcr1-il-8r-in-macrophages-utilizing-cell-surface-tnfr1-and-il-1-receptor-during-staphylococcus-aureus-infection
#18
Biswadev Bishayi, Rana Adhikary, Sahin Sultana, Rajen Dey, Ajeya Nandi
Currently, very few studies are available on the expression of CXCR1 in mouse macrophages having both intact TNFR1 and IL-1R or their deficiency in relation to acute S. aureus infection. Peritoneal macrophages from mice neutralized singly for TNFR1or IL-1R, or for both TNFR1 and IL-1R were infected with S. aureus in vitro and their ability to secrete cytokines and reactive oxygen species (ROS) were determined. It was observed that the release TNF-α and IL-1β in response to S. aureus infection was decreased in macrophages when both TNFR1 and IL-1R were neutralized...
November 18, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/29158612/detection-of-pathological-changes-in-the-aorta-during-thoracic-aortic-aneurysm-progression-on-molecular-level
#19
Miroslava Rabajdová, Peter Urban, Ivana Špaková, Artemiou Panagiotis, Michaela Ferenčáková, Dušan Rybár, Nikita Bobrov, František Sabol, Mária Mareková
The progression of thoracic aortic aneurysm depends on regulation of aortic wall homeostasis and on changes in the structural components of the extracellular matrix, which are affected by multiple molecular signalling pathways. We decided to correlate the diameter of ascending thoracic aneurysm with gene expression of inflammation markers (IL-6, CRP), cytokine receptors (IL-6R, TNFR1, and TNFR2), and extracellular matrix components (Emilin-1, MMP9, and TIMP) for detection of the degree of pathological process of TAA formation...
2017: Disease Markers
https://www.readbyqxmd.com/read/29155425/granulocyte-derived-tnf%C3%AE-promotes-vascular-and-hematopoietic-regeneration-in-the-bone-marrow
#20
Emily Bowers, Anastasiya Slaughter, Paul S Frenette, Rork Kuick, Oscar M Pello, Daniel Lucas
Endothelial cells are a critical component of the bone marrow (BM) stromal network, which maintains and regulates hematopoietic cells. Vascular regeneration precedes, and is necessary for, successful hematopoietic stem cell (HSC) transplantation, the only cure for most hematopoietic diseases. Recent data suggest that mature hematopoietic cells regulate BM stromal-cell function. Whether a similar cross-talk regulates the BM vasculature is not known. Here we found that donor hematopoietic cells act on sinusoidal endothelial cells and induce host blood vessel and hematopoietic regeneration after BM transplantation in mice...
November 20, 2017: Nature Medicine
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