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https://www.readbyqxmd.com/read/28882891/identification-of-optineurin-as-an-interleukin-1-receptor-associated-kinase-1-binding-protein-and-its-role-in-regulation-of-myd88-dependent-signaling
#1
Mitsuyoshi Tanishima, Shigeo Takashima, Arata Honda, Daisuke Yasuda, Takashi Tanikawa, Satoshi Ishii, Takashi MaruYama
Upon stimulation of toll-like receptor (TLR) with various microbial ligands, induction of a variety of inflammatory genes is elicited by activation of a myeloid differentiation primary-response protein 88 (MyD88)-dependent signaling pathway. Interleukin-1 (IL-1) receptor-associated kinase 1 (IRAK1) plays an essential role in this pathway by activating nuclear factor κB (NF-κB) and mitogen-activated kinases (MAPK). Here, we identified optineurin (OPTN) as an IRAK1-binding protein by yeast two-hybrid screening using IRAK1 as bait...
September 7, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28877954/suppression-of-toll-like-receptor-2-mediated-proinflammatory-responses-by-mycobacterium-tuberculosis-protein-rv3529c
#2
Upasana Bandyopadhyay, Attinder Chadha, Priya Gupta, Brijendra Tiwari, Kausik Bhattacharyya, Sonam Popli, Rajagopal Raman, Vani Brahamachari, Yogendra Singh, Pawan Malhotra, Krishnamurthy Natarajan
Microorganisms are known to devise various strategies to thwart protective responses by the host. One such strategy is to incorporate sequences and domains in their genes/proteins that have similarity to various domains of the host proteins. In this study, we report that Mycobacterium tuberculosis protein Rv3529c exhibits significant similarity to the death domain of the TLR pathway adaptor protein MyD88. Incubation of macrophages with Rv3529c specifically inhibited TLR2-mediated proinflammatory responses. This included attenuated oxidative burst, reduced phosphorylation of MAPK-ERK, reduced activation of transcription factor NF-κB and reduced secretion of proinflammatory cytokines IFN-γ, IL-6, and IL-17A with a concomitant increased secretion of suppressor cytokines IL-10 and TGF-β...
September 6, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28858844/can-regular-moderate-exercise-lead-to-changes-in-mirna-146a-and-its-adapter-proteins-in-the-kidney-of-streptozotocin-induced-diabetic-male-rats
#3
H Oghbaei, N Ahmadi Asl, F Sheikhzadeh
OBJECTIVE: The aim of this study was to assess whether microRNA-146a and its adapter proteins TNF receptor associated factor6 (TRAF6) and interleukin-1 receptor-associated kinase-1 (IRAK1) may be changed in the kidney of streptozotocin-induced diabetic rats, following regular moderate exercise. METHODS: Forty adult male Wistar rats were allocated randomly into four groups (n=10), including sedentary control (SC), sedentary diabetic (SD), healthy sixty-day exercise (H60E), and diabetic sixty-day exercise (D60E) groups...
July 1, 2017: Endocrine Regulations
https://www.readbyqxmd.com/read/28844021/tlr2-tlr3-and-tlr5-regulation-of-pro-inflammatory-and-pro-labour-mediators-in-human-primary-myometrial-cells
#4
Ratana Lim, Gillian Barker, Martha Lappas
Preterm birth continues to be a significant global health care issue, due to our lack of understanding of the mechanisms that drive human labour and delivery. Toll-like receptors (TLRs) are essential in triggering an inflammatory response in human gestational tissues, leading to the production of pro-inflammatory and pro-labour mediators, and thus preterm birth. The aims of this study were to determine whether the adaptor molecules associated with TLR2, TLR3 and TLR5 signalling are involved in human myometrium...
August 24, 2017: Journal of Reproductive Immunology
https://www.readbyqxmd.com/read/28811005/regulatory-effects-of-mir-146a-b-on-the-function-of-endothelial-progenitor-cells-in-acute-ischemic-stroke-in-mice
#5
Zeng-Feng Su, Zhong-Wu Sun, Ying Zhang, Shu Wang, Qi-Gui Yu, Ze-Bing Wu
The study aims to explore how microRNA-146a/b (miR-146a/b) regulates the function of endothelial progenitor cells (EPCs) in acute ischemic stroke in mice. Eighty male SPF C57BL/6J mice were evenly divided into the model-6 h, model-12 h, model-24 h (mice suffered from middle cerebral artery occlusion [MCAO] for 6 h, 12 h and model-24 h) and normal groups. EPCs were transfected and assigned into the control, MCAO, MCAO-miR-146a, MCAO-miR-146b and MCAO-miR-146a/b groups. The qRT-PCR was used to detect miR-146a/b expression in EPCs...
August 2017: Kaohsiung Journal of Medical Sciences
https://www.readbyqxmd.com/read/28780618/upregulated-irak1-and-irak4-promoting-the-production-of-ifn-%C3%AE-and-il-17-in-behcet-s-disease
#6
Min Sun, Peizeng Yang, Yan Yang, Jian Ye
PURPOSE: To investigate the expression and function of IRAK1 and IRAK4 involved in the development of Behcet's disease. METHODS: Twenty-eight Behcet's patients and thirty-two normal subjects were involved in this study. The mRNA levels of IRAK1 and IRAK4 from active Behcet's patients, inactive Behcet's patients and normal controls were detected using real-time quantitative PCR. CD4(+)T cells were extracted from peripheral blood mononuclear cells of active Behcet's patients and normal controls...
August 5, 2017: International Ophthalmology
https://www.readbyqxmd.com/read/28775099/alternative-pre-mrna-splicing-of-toll-like-receptor-signaling-components-in-peripheral-blood-mononuclear-cells-from-ards-patients
#7
Rachel Z Blumhagen, Brenna R Hedin, Kenneth C Malcolm, Ellen L Burnham, Marc Moss, Edward Abraham, Tristan J Huie, Jerry A Nick, Tasha E Fingerlin, Scott Alper
A key physiological feature of Acute Respiratory Distress Syndrome (ARDS) is inflammation. Toll-like receptor (TLR) signaling is required to combat the infection that underlies many ARDS cases but also contributes to pathological inflammation. Several TLR signaling pathway genes encoding positive effectors of inflammation also produce alternatively spliced mRNAs encoding negative regulators of inflammation. An imbalance between these isoforms could contribute to pathological inflammation and disease severity...
August 3, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28775078/tlr2-plays-a-key-role-in-platelet-hyperreactivity-and-accelerated-thrombosis-associated-with-hyperlipidemia
#8
Sudipta Biswas, Alejandro Zimman, Detao Gao, Tatiana Byzova, Eugene Podrez
Rationale: Platelet hyperreactivity, which is common in many pathological conditions, is associated with increased atherothrombotic risk. The mechanisms leading to platelet hyperreactivity are complex and not yet fully understood. Objective: Platelet hyperreactivity and accelerated thrombosis, specifically in dyslipidemia, have been mechanistically linked to accumulation in the circulation of a specific group of oxidized phospholipids (oxPCCD36) that are ligands for the platelet pattern-recognition receptor CD36...
August 3, 2017: Circulation Research
https://www.readbyqxmd.com/read/28757040/porcine-parvovirus-infection-activates-inflammatory-cytokine-production-through-toll-like-receptor-9-and-nf-%C3%AE%C2%BAb-signaling-pathways-in-porcine-kidney-cells
#9
Yong Zhou, Xiao-Hui Jin, Ya-Xing Jing, Yue Song, Xiao-Xiang He, Lan-Lan Zheng, Ya-Bin Wang, Zhan-Yong Wei, Gai-Ping Zhang
Porcine parvovirus virus (PPV) is an animal virus that has caused high economic losses for the swine industry worldwide. Previous studies demonstrated that PPV infection induced significant production of interleukin 6 (IL-6) in vitro and in vivo. However, the inflammatory cytokines and specific signaling pathways induced during PPV infection remain largely unknown. In the present study, we analyzed the expression levels of IL-6 in PPV-infected porcine kidney 15 (PK-15) and the results showed that PPV infection induced the increase of IL-6 mRNA expression in a dose-dependent manner...
August 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/28739486/microrna-146a-5p-attenuates-liver-fibrosis-by-suppressing-profibrogenic-effects-of-tgf%C3%AE-1-and-lipopolysaccharide
#10
Yanting Zou, Yu Cai, Di Lu, Yi Zhou, Qunyan Yao, Shuncai Zhang
Liver fibrosis is characterized by proliferation and activation of hepatic stellate cells (HSCs). Transforming growth factor-β1 (TGFβ1) is crucial for liver fibrogenesis, and gut-derived endotoxin (LPS) also plays an important role in liver fibrogenesis. In the present study, we found that microRNA-146a-5p (miR-146a-5p) could regulate TGFβ1/Smad and LPS/NF-κB/Bambi pathways to attenuate liver fibrosis. Downregulated miR-146a-5p and upregulated level of LPS were found in liver of CCl4-treated rats. On cellular level, expression of miR-146a-5p is reduced during primary rat HSCs naturally activation and changed in response to TGFβ1 and/or LPS stimulation in primary rat HSCs and human HSC line LX-2...
November 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28731142/nlrc3-promotes-host-resistance-against-pseudomonas-aeruginosa-induced-keratitis-by-promoting-the-degradation-of-irak1
#11
Litao Guo, Qingzhu Kong, Zhijun Dong, Weili Dong, Xiaoxiao Fu, Leqi Su, Xiaobo Tan
Pseudomonas aeruginosa (PA)-induced keratitis is one of the most common and destructive bacterial diseases. The pathogenesis of PA infections is closely associated with excessive inflammatory responses. Nucleotide oligomerization domain (NOD)-like receptor (NLR) family with caspase activation and recruitment domain (CARD) containing 3 (NLRC3) protein has been implicated as a negative regulator of inflammation and antiviral response, but the role of NLRC3 in PA-induced keratitis has not been described...
July 20, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28714001/lps-enhances-tlr4-expression-and-ifn%C3%A2-%C3%AE-production-via-the-tlr4-irak-nf%C3%A2-%C3%AE%C2%BAb-signaling-pathway-in-rat-pulmonary-arterial-smooth-muscle-cells
#12
Pengyan Wang, Xuhui Han, Biwen Mo, Guojin Huang, Changming Wang
The aim of the present study was to investigate the role of the Toll‑like receptor (TLR)4 signaling pathway in cellular response to lipopolysaccharide (LPS) in rat pulmonary artery smooth muscle cells (PASMCs). Chronic obstructive pulmonary disease (COPD) rats were established with passive inhaling cigarette smoke plus injection of LPS. The TLR4 protein in lung tissues was determined with immunohistochemical staining and protein levels of the components of the TLR4 pathway in PASMCs were analyzed with western blotting...
September 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28684329/house-dust-mite-increases-pro-th2-cytokines-il-25-and-il-33-via-the-activation-of-tlr1-6-signaling
#13
Yong Hyun Jang, Jin Kyeong Choi, Meiling Jin, Young-Ae Choi, Zae Young Ryoo, Hyun-Shik Lee, Pil-Hoon Park, Sun-Uk Kim, Taeg Kyu Kwon, Myoung Ho Jang, Sin-Hyeog Im, Sun Young Moon, Weon Ju Lee, Seok-Jong Lee, Do Won Kim, Sang-Hyun Kim
House dust mite (HDM) has been implicated in the etiology and exacerbation of atopic dermatitis (AD). Diverse factors contribute to HDM allergenicity through the activation of innate immunity. We investigated whether Dermatophagoides farinae extract (DFE) allergens mediate innate immune activation through specific Toll-like receptors (TLRs) in epidermal keratinocytes, DFE-induced murine AD model and human AD lesions. DFE activated the expression of TLR1, TLR6, interleukin (IL)-25, and IL-33 in human primary keratinocytes and HaCaT cells...
July 3, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28680194/syk-plays-a-critical-role-in-the-expression-and-activation-of-irak1-in-lps-treated-macrophages
#14
Jae Gwang Park, Young-Jin Son, Byong Chul Yoo, Woo Seok Yang, Ji Hye Kim, Jong-Hoon Kim, Jae Youl Cho
To address how interleukin-1 receptor-associated kinase 1 (IRAK1) is controlled by other enzymes activated by toll-like receptor (TLR) 4, we investigated the possibility that spleen tyrosine kinase (Syk), a protein tyrosine kinase that is activated at an earlier stage during TLR4 activation, plays a central role in regulating the functional activation of IRAK1. Indeed, we found that overexpression of myeloid differentiation primary response gene 88 (MyD88), an adaptor molecule that drives TLR signaling, induced IRAK1 expression and that piceatannol, a Syk inhibitor, successfully suppressed the MyD88-dependent upregulation of IRAK1 under LPS treatment conditions...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28668488/glycyrrhetinic-acid-prevents-acetaminophen-induced-acute-liver-injury-via-the-inhibition-of-cyp2e1-expression-and-hmgb1-tlr4-signal-activation-in-mice
#15
Genling Yang, Li Zhang, Li Ma, Rong Jiang, Ge Kuang, Ke Li, Hongtao Tie, Bin Wang, Xinyu Chen, Tianjun Xie, Xia Gong, Jingyuan Wan
Acetaminophen (APAP) is a widely used antipyretic and analgesic drug, which is safe and effective at the therapeutic dose. Unfortunately, excessive dosage of APAP could cause severe liver injury due to lack of effective therapy. Successful therapeutic strategies are urgently requested in clinic. Glycyrrhetinic acid (GA), derived from a traditional medicine licorice, has been shown to exert anti-inflammatory and antioxidant actions. In this study, the effect and the underlying mechanism of GA on APAP-induced hepatotoxicity were explored...
June 29, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28659487/mumps-virus-sh-protein-inhibits-nf-%C3%AE%C2%BAb-activation-by-interacting-with-tumor-necrosis-factor-receptor-1-interleukin-1-receptor-1-and-toll-like-receptor-3-complexes
#16
Stephanie Franz, Paul Rennert, Maria Woznik, Josephine Grützke, Amy Lüdde, Eva Maria Arriero Pais, Tim Finsterbusch, Henriette Geyer, Annette Mankertz, Nicole Friedrich
The mumps virus (MuV) small hydrophobic protein (SH) is a type I membrane protein expressed in infected cells. SH has been reported to interfere with innate immunity by inhibiting tumor necrosis factor alpha (TNF-α)-mediated apoptosis and NF-κB activation. To elucidate the underlying mechanism, we generated recombinant MuVs (rMuVs) expressing the SH protein with an N-terminal FLAG epitope or lacking SH expression due to the insertion of three stop codons into the SH gene. Using these viruses, we were able to show that SH reduces the phosphorylation of IKKβ, IκBα, and p65 as well as the translocation of p65 into the nucleus of infected A549 cells...
September 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28659029/the-mixture-of-anemarrhena-asphodeloides-and-coptis-chinensis-attenuates-high-fat-diet-induced-colitis-in-mice
#17
Su-Min Lim, Hyun-Sik Choi, Dong-Hyun Kim
Anemarrhena asphodeloides (AA, family Liliaceae) inhibits macrophage activation by inhibiting IRAK1 phosphorylation and helper T (Th)17 differentiation. Coptis chinensis (CC, family Ranunculaceae), which inhibits macrophage activation by inhibiting the binding of lipopolysaccharide (LPS) on toll-like receptor 4 and inducing regulatory T (Treg) cell differentiation. The mixture of AA and CC (AC-mix) synergistically attenuates 2,4,6-trinitrobenzenesulfonic acid or dextran sulfate sodium-induced colitis in mice by inhibiting NF-[Formula: see text]B activation and regulating Th17/Treg balance...
June 28, 2017: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/28587864/up-regulation-of-circulating-mirna146a-correlates-with-viral-load-via-irak1-and-traf6-in-hepatitis-c-virus-infected-patients
#18
Fayda Ibrahim Abdel Motaleb, Enas Samir Nabih, Sherif Moneir Mohamed, Nehal Samir Abd Elhalim
BACKGROUND: Hepatitis C virus (HCV) is a life threatening human pathogen. It has been found that miRNA146a regulates innate immunity, inflammatory response and antiviral pathway. We evaluated miRNA146a expression by real-time PCR and IL-1 receptor associated kinase 1 (IRAK1) and TNF receptor-associated factor 6 (TRAF6) levels by ELISA in serum of 36 HCV viremia patients and 42 age and gender matched healthy controls. RESULTS: miRNA146a expression was significantly higher in HCV patients with a best cut off value 1...
June 3, 2017: Virus Research
https://www.readbyqxmd.com/read/28572512/deletion-of-interleukin-1-receptor-associated-kinase-1-irak1-improves-glucose-tolerance-primarily-by-increasing-insulin-sensitivity-in-skeletal-muscle
#19
Xiao-Jian Sun, Soohyun Park Kim, Dongming Zhang, Helen Sun, Qi Cao, Xin Lu, Zhekang Ying, Liwu Li, Robert R Henry, Theodore P Ciaraldi, Simeon I Taylor, Michael J Quon
Chronic inflammation may contribute to insulin resistance via molecular cross-talk between pathways for pro-inflammatory and insulin signaling. Interleukin 1 receptor-associated kinase 1 (IRAK-1) mediates pro-inflammatory signaling via IL-1 receptor/Toll-like receptors, which may contribute to insulin resistance, but this hypothesis is untested. Here, we used male Irak1 null (k/o) mice to investigate the metabolic role of IRAK-1. C57BL/6 wild-type (WT) and k/o mice had comparable body weights on low-fat and high-fat diets (LFD and HFD, respectively)...
July 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28553204/leucine-rich-repeat-kinase-2-lrrk2-stimulates-il-1%C3%AE-mediated-inflammatory-signaling-through-phosphorylation-of-rcan1
#20
Kyung A Han, Lang Yoo, Jee Y Sung, Sun A Chung, Ji W Um, Hyeyoung Kim, Wongi Seol, Kwang C Chung
Leucine-rich repeat kinase 2 (LRRK2) is a Ser/Thr kinase having mixed lineage kinase-like and GTPase domains, controlling neurite outgrowth and neuronal cell death. Evidence suggests that LRRK2 is involved in innate immune response signaling, but the underlying mechanism is yet unknown. A novel protein inhibitor of phosphatase 3B, RCAN1, is known to positively regulate inflammatory signaling through modulation of several intracellular targets of interleukins in immune cells. In the present study, we report that LRRK2 phosphorylates RCAN1 (RCAN1-1S) and is markedly up-regulated during interleukin-1β (IL-1β) treatment...
2017: Frontiers in Cellular Neuroscience
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