keyword
MENU ▼
Read by QxMD icon Read
search

Irak4

keyword
https://www.readbyqxmd.com/read/27895398/dysregulation-of-innate-immunity-in-ulcerative-colitis-patients-who-fail-anti-tumor-necrosis-factor-therapy
#1
Angela C Baird, Dominic Mallon, Graham Radford-Smith, Julien Boyer, Thierry Piche, Susan L Prescott, Ian C Lawrance, Meri K Tulic
AIM: To study the innate immune function in ulcerative colitis (UC) patients who fail to respond to anti-tumor necrosis factor (TNF) therapy. METHODS: Effects of anti-TNF therapy, inflammation and medications on innate immune function were assessed by measuring peripheral blood mononuclear cell (PBMC) cytokine expression from 18 inflammatory bowel disease patients pre- and 3 mo post-anti-TNF therapy. Toll-like receptor (TLR) expression and cytokine production post TLR stimulation was assessed in UC "responders" (n = 12) and "non-responders" (n = 12) and compared to healthy controls (n = 12)...
November 7, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/27890916/polydatin-ameliorates-staphylococcus-aureus-induced-mastitis-in-mice-via-inhibiting-tlr2-mediated-activation-of-the-p38-mapk-nf-%C3%AE%C2%BAb-pathway
#2
Kang-Feng Jiang, Gan Zhao, Gan-Zhen Deng, Hai-Chong Wu, Nan-Nan Yin, Xiu-Ying Chen, Chang-Wei Qiu, Xiu-Li Peng
Recent studies show that Polydatin (PD) extracted from the roots of Polygonum cuspidatum Sieb, a widely used traditional Chinese remedies, possesses anti-inflammatory activity in several experimental models. In this study, we investigated the anti-inflammatory effects of PD on Staphylococcus aureus-induced mastitis in mice and elucidated the potential mechanisms. In mice with S aureus-induced mastitis, administration of PD (15, 30, 45 mg/kg, ip) or dexamethasone (Dex, 5 mg/kg, ip) significantly suppressed the infiltration of inflammatory cells, ameliorated the mammary structural damage, and inhibited the activity of myeloperoxidase, a biomarker of neutrophils accumulation...
November 28, 2016: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/27881653/microrna-373-facilitated-the-replication-of-porcine-reproductive-and-respiratory-syndrome-virus-prrsv-by-its-negative-regulation-of-type-i-interferon-induction
#3
Jing Chen, Xibao Shi, Xiaozhuan Zhang, Aiping Wang, Li Wang, Yanyan Yang, Ruiguang Deng, Gai-Ping Zhang
: microRNAs (miRNAs) played an important role in the regulation of immune response. Previous studies have indicated that dysregulating the miRNAs may lead to the immunosuppression of porcine reproductive and respiratory syndrome virus (PRRSV). However, it's not clear about how PRRSV regulated the expression of host miRNA which may make the immune escape or promote the replication of the virus. The present work suggested that PRRSV up-regulated the expression of miR-373 through elevating the expression of specificity protein 1 (Sp1) in MARC-145 cells...
November 23, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27869651/pericyte-myd88-and-irak4-control-inflammatory-and-fibrotic-responses-to-tissue-injury
#4
Irina A Leaf, Shunsaku Nakagawa, Bryce G Johnson, Jin Joo Cha, Kristen Mittelsteadt, Kevin M Guckian, Ivan G Gomez, William A Altemeier, Jeremy S Duffield
Fibrotic disease is associated with matrix deposition that results in the loss of organ function. Pericytes, the precursors of myofibroblasts, are a source of pathological matrix collagens and may be promising targets for treating fibrogenesis. Here, we have shown that pericytes activate a TLR2/4- and MyD88-dependent proinflammatory program in response to tissue injury. Similarly to classic immune cells, pericytes activate the NLRP3 inflammasome, leading to IL-1β and IL-18 secretion. Released IL-1β signals through pericyte MyD88 to amplify this response...
November 21, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27864528/irak1-and-irak4-promote-phosphorylation-ubiquitination-and-degradation-of-myd88-adaptor-like-mal
#5
Aisling Dunne, Susan Carpenter, Constantinos Brikos, Pearl Gray, Astrid Strelow, Holger Wesche, Nick Morrice, Luke A J O'Neill
No abstract text is available yet for this article.
November 18, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27845762/recent-progress-in-the-molecular-recognition-and-therapeutic-importance-of-interleukin-1-receptor-associated-kinase-4
#6
REVIEW
Mahesh Chandra Patra, Sangdun Choi
Toll-like receptors (TLRs) are the most upstream pattern recognition receptors in the cell, which detect pathogen associated molecular patterns and initiate signal transduction, culminating in the transcription of pro-inflammatory cytokines and antiviral interferon. Interleukin-1 receptor-associated kinase 4 (IRAK4) is a key mediator in TLR (except for TLR3) and interleukin-1 receptor signaling pathways. The loss of kinase function of IRAK4 is associated with increased susceptibility to various pathogens, while its over-activation causes autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, and cancer...
November 13, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27807192/suppression-of-irak1-or-irak4-catalytic-activity-but-not-type-1-ifn-signaling-prevents-lupus-nephritis-in-mice-expressing-a-ubiquitin-binding-defective-mutant-of-abin1
#7
Sambit K Nanda, Marta Lopez-Pelaez, J Simon C Arthur, Francesco Marchesi, Philip Cohen
Polymorphisms in the TNIP1 gene encoding A20-binding inhibitor of NF-κB1 (ABIN1) predispose to lupus and other autoimmune diseases in at least eight human populations. We found previously that knock-in mice expressing a ubiquitin-binding-defective mutant of ABIN1 (ABIN1[D485N]) develop autoimmunity as they age and succumb to a disease resembling lupus nephritis in humans. In this article, we report that Flt3-derived dendritic cells from these mice overproduced type 1 IFNs upon stimulation with ligands that activate TLR7 or TLR9...
December 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27702822/constitutive-irak4-activation-underlies-poor-prognosis-and-chemoresistance-in-pancreatic-ductal-adenocarcinoma
#8
Daoxiang Zhang, Lin Li, Hongmei Jiang, Brett Knolhoff, Albert C Lockhart, Andrea Wang-Gillam, David DeNardo, Marianna B Ruzinova, Kian-Huat Lim
PURPOSE: Aberrant activation of the NF-κB transcription factors underlies the aggressive behavior and poor outcome of pancreatic ductal adenocarcinoma (PDAC). However, clinically effective and safe NF-κB inhibitors are not yet available. Because NF-κB transcription factors can be activated by the Interleukin-1 Receptor-Associated Kinase (IRAK) downstream of the Toll-like receptors (TLRs), but has not been explored in PDAC, we sought to investigate the role of IRAK in the pathobiology of PDAC...
October 4, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27676214/tlr4-acts-as-a-death-receptor-for-ultraviolet-radiation-uvr-through-irak-independent-and-fadd-dependent-pathway-in-macrophages
#9
Hua Zhou, Erin Harberts, Rita Fishelevich, Anthony A Gaspari
UVR-induced apoptosis in cutaneous antigen presenting cells (APC) causes systemic immune suppression and is dependent on TLR4/MyD88 signaling, but the apoptotic signaling pathways have not been defined. Macrophages pre-treated with lipopolysaccharide (LPS) were unresponsive to subsequent LPS treatment; however, but were susceptible to UVR-induced apoptosis. Macrophage survival and apoptotic events after UVR were also unaffected by treatment with TLR4 antagonists, a blocking IgG or a TLR4 analog antagonist, suggesting that UVR cell death is independent of a soluble ligand...
September 27, 2016: Experimental Dermatology
https://www.readbyqxmd.com/read/27624059/paeonol-suppresses-neuroinflammatory-responses-in-lps-activated-microglia-cells
#10
Li Xia He, Xiaoyun Tong, Jing Zeng, Yuanqing Tu, Saicun Wu, Manping Li, Huaming Deng, Miaomiao Zhu, Xiucun Li, Hong Nie, Li Yang, Feng Huang
In this work, we assessed the anti-inflammatory effects of paeonol (PAE) in LPS-activated N9 microglia cells, as well as its underlying molecular mechanisms. PAE had no adverse effect on the viability of murine microglia N9 cell line within a broad range (0.12∼75 μM). When N9 cell line was activated by LPS, PAE (0.6, 3, 15 μM) significantly suppressed the release of proinflammatory products, such as nitric oxide (NO), interleukin-1β (IL-1β), and prostaglandin E2 (PGE2), demonstrated by the ELISA assay...
December 2016: Inflammation
https://www.readbyqxmd.com/read/27579619/i%C3%AE%C2%BAb%C3%AE-an-emerging-player-in-cancer
#11
Marie Willems, Nadège Dubois, Lucia Musumeci, Vincent Bours, Pierre A Robe
IκBζ, an atypical member of the nuclear IκB family of proteins, is expressed at low levels in most resting cells, but is induced upon stimulation of Toll-like/IL-1 receptors through an IRAK1/IRAK4/NFκB-dependent pathway. Like its homolog Bcl3, IκBζ can regulate the transcription of a set of inflamatory genes through its association with the p50 or p52 subunits of NF-κB. Long studied as a key component of the immune response, IκBζ emerges as an important regulator of inflammation, cell proliferation and survival...
August 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27476420/efforts-towards-the-optimization-of-a-bi-aryl-class-of-potent-irak4-inhibitors
#12
Jennifer Hanisak, W Michael Seganish, William T McElroy, Haiquin Tang, Rui Zhang, Hon-Chung Tsui, Theirry Fischmann, Deen Tulshian, James Tata, Christopher Sondey, Kristine Devito, James Fossetta, Charles G Garlisi, Daniel Lundell, Xiaoda Niu
IRAK4 has been identified as potential therapeutic target for inflammatory and autoimmune diseases. Herein we report the identification and initial SAR studies of a new class of pyrazole containing IRAK4 inhibitors designed to expand chemical diversity and improve off target activity of a previously identified series. These compounds maintain potent IRAK4 activity and desirable ligand efficiency. Rat clearance and a variety of off target activities were also examined, resulting in encouraging data with tractable SAR...
September 1, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27432718/variation-of-46-innate-immune-genes-evaluated-for-their-contribution-in-pneumococcal-meningitis-susceptibility-and-outcome
#13
Bart Ferwerda, Mercedes Valls Serón, Aldo Jongejan, Aeilko H Zwinderman, Madelijn Geldhoff, Arie van der Ende, Frank Baas, Matthijs C Brouwer, Diederik van de Beek
Pneumococcal meningitis is the most common and severe form of bacterial meningitis. Early recognition of the pathogen and subsequent innate immune response play a vital role in disease susceptibility and outcome. Genetic variations in innate immune genes can alter the immune response and influence susceptibility and outcome of meningitis disease. Here we conducted a sequencing study of coding regions from 46 innate immune genes in 435 pneumococcal meningitis patients and 416 controls, to determine the role of genetic variation on pneumococcal meningitis susceptibility and disease outcome...
August 2016: EBioMedicine
https://www.readbyqxmd.com/read/27310003/inhibitors-of-interleukin-1-receptor-associated-kinase-4-irak4-a-patent-review-2012-2015
#14
W Michael Seganish
INTRODUCTION: IRAK4 is located proximal to TLR/IL-1 receptors, and in preclinical studies, inhibits downstream signaling from these receptors. The development of novel small molecule inhibitors of this kinase has the potential to lead to new therapeutics to treat diseases such as rheumatoid arthritis, lupus, and lymphomas. AREAS COVERED: The aim of this review is to summarize the recent patent literature (2012-2015) surrounding small molecule inhibitors of IRAK4...
August 2016: Expert Opinion on Therapeutic Patents
https://www.readbyqxmd.com/read/27270491/irak-regulates-macrophage-foam-cell-formation-by-modulating-genes-involved-in-cholesterol-uptake-and-efflux
#15
Minakshi Rana, Amit Kumar, Rajiv Lochan Tiwari, Vishal Singh, Tulika Chandra, Madhu Dikshit, Manoj Kumar Barthwal
Interleukin-1 receptor-associated kinase-1 (IRAK1) is linked to the pathogenesis of atherosclerosis; however, its role in macrophage foam cell formation is not known. Therefore, the present study investigated the role of IRAK1 in lipid uptake, biosynthesis, and efflux in THP-1 derived macrophages and human monocyte-derived macrophages (HMDMs). Ox-LDL (40 μg/mL, 15 minutes-48 hours) treatment induced time-dependent increase in IRAK1, IRAK4, and Stat1 activation in THP-1 derived macrophages. IRAK1/4 inhibitor (INH) or IRAK1 siRNA significantly attenuated cholesterol accumulation, DiI-Ox-LDL binding, and uptake while cholesterol efflux to apoAI and HDL was enhanced in THP-1 derived macrophages and HMDMs...
July 2016: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/27270216/cinnamaldehyde-and-allopurinol-reduce-fructose-induced-cardiac-inflammation-and-fibrosis-by-attenuating-cd36-mediated-tlr4-6-irak4-1-signaling-to-suppress-nlrp3-inflammasome-activation
#16
Lin-Lin Kang, Dong-Mei Zhang, Chun-Hua Ma, Jian-Hua Zhang, Ke-Ke Jia, Jia-Hui Liu, Rong Wang, Ling-Dong Kong
Fructose consumption induces metabolic syndrome to increase cardiovascular disease risk. Cinnamaldehyde and allopurinol possess anti-oxidative and anti-inflammatory activity to relieve heart injury in metabolic syndrome. But the mechanisms of fructose-induced cardiac injury, and cardioprotective effects of cinnamaldehyde and allopurinol are not completely understood. In this study, fructose-fed rats displayed metabolic syndrome with elevated serum ox-LDL, cardiac oxidative stress, inflammation and fibrosis...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27260481/inflammasome-and-toll-like-receptor-signaling-in-human-monocytes-after-successful-cardiopulmonary-resuscitation
#17
Alexander Asmussen, Katrin Fink, Hans-Jörg Busch, Thomas Helbing, Natascha Bourgeois, Christoph Bode, Sebastian Grundmann
BACKGROUND: Whole body ischemia-reperfusion injury (IRI) after cardiopulmonary resuscitation (CPR) induces a generalized inflammatory response which contributes to the development of post-cardiac arrest syndrome (PCAS). Recently, pattern recognition receptors (PRRs), such as toll-like receptors (TLRs) and inflammasomes, have been shown to mediate the inflammatory response in IRI. In this study we investigated monocyte PRR signaling and function in PCAS. METHODS: Blood samples were drawn in the first 12 hours, and at 24 and 48 hours following return of spontaneous circulation in 51 survivors after cardiac arrest...
2016: Critical Care: the Official Journal of the Critical Care Forum
https://www.readbyqxmd.com/read/27224911/increased-translocation-of-antigens-to-endosomes-and-tlr4-mediated-endosomal-recruitment-of-tap-contribute-to-nicotine-augmented-cross-presentation
#18
Yan Yan Wang, Chun Fang Hu, Juan Li, Xiang You, Feng Guang Gao
Cross-presentation by dendritic cells (DCs) requires surface molecules such as lectin, CD40, langerin, heat shock protein, mannose receptor, mediated endocytosis, the endosomal translocation of internalized antigen, and the relocation of transporter associated with antigen processing (TAP). Although the activation of α7 nicotinic acetylcholine receptor (α7 nAchR) up-regulate surface molecule expression, augment endocytosis, and enhance cross-presentation, the molecular mechanism of α7 nAchR activation-increased cross-presentation is still poorly understood...
June 21, 2016: Oncotarget
https://www.readbyqxmd.com/read/27181127/celastrol-targets-iraks-to-block-toll-like-receptor-4-mediated-nuclear-factor-%C3%AE%C2%BAb-activation
#19
Yu-fan Shen, Xue Zhang, Ying Wang, Fan-fan Cao, Georges Uzan, Bin Peng, Deng-hai Zhang
OBJECTIVE: Celastrol has been established as a nuclear factor-κB (NF-κB) activation inhibitor; however, the exact mechanism behind this action is still unknown. Using text-mining technology, the authors predicted that interleukin-1 receptor-associated kinases (IRAKs) are potential celastrol targets, and hypothesized that targeting IRAKs might be one way that celastrol inhibits NF-κB. This is because IRAKs are key molecules for some crucial pathways to activate NF-κB (e.g., the interleukin-1 receptor (IL-1R)/Toll-like receptor (TLR) superfamily)...
May 2016: Journal of Integrative Medicine
https://www.readbyqxmd.com/read/27158377/relation-between-anti-atherosclerotic-effects-of-irak4-and-modulation-of-vascular-smooth-muscle-cell-phenotype-in-diabetic-rats
#20
Lijuan Cao, Defeng Pan, Dongye Li, Yanbin Zhang, Qiuping Chen, Tongda Xu, Wenhua Li, Wanling Wu
Deregulation of phenotypic modulation in VSMCs is the initial stage of atherosclerosis, especially in diabetes. Functional deficiency of IRAK4 inhibits the formation of vascular lesions in ApoE-/- mice. Therefore, in this study, we examined the functions of IRAK4 in the regulation of VSMCs differentiation and phenotypic modulation at the levels of transcription and translation in T2D rats. The T2D rat model was generated by feeding a high-fat diet and injecting a low dose of streptozotocin intraperitoneally...
2016: American Journal of Translational Research
keyword
keyword
70304
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"