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https://www.readbyqxmd.com/read/29796309/deubiquitinase-function-of-a20-maintains-and-repairs-endothelial-barrier-after-lung-vascular-injury
#1
Dheeraj Soni, Dong-Mei Wang, Sushil C Regmi, Manish Mittal, Stephen M Vogel, Dirk Schlüter, Chinnaswamy Tiruppathi
Vascular endothelial cadherin (VE-cad) expression at endothelial adherens junctions (AJs) regulates vascular homeostasis. Here we show that endothelial A20 is required for VE-cad expression at AJs to maintain and repair the injured endothelial barrier. In endothelial cell (EC)-restricted Tnfaip3 (A20) knockout ( A20 ∆EC ) mice, LPS challenge caused uncontrolled lung vascular leak and persistent sequestration of polymorphonuclear neutrophil (PMNs). Importantly, A20 ∆EC mice exhibited drastically reduced VE-cad expression in lungs compared with wild-type counterparts...
2018: Cell Death Discovery
https://www.readbyqxmd.com/read/29717720/ouabain-attenuates-sepsis-induced-immunosuppression-in-mice-by-activation-and-anti-apoptosis-of-t-cells
#2
Ruibin Niu, Hao Gao, Yuan Zhou, Jie Zhang
BACKGROUND Sepsis is known to trigger impaired T cell function, which relates to immunosuppression, contributing to refractory infection and high mortality. The mechanisms of T cell recovery remain to be elucidated, and novel and effective therapeutics for sepsis are needed. Ouabain, a small molecule of cardiac glycosides, can reverse immunoparalysis in many settings. MATERIAL AND METHODS Our study was designed to determine if ouabain can relieve sepsis by modulating T cell response and related pathways. The "two-hit" model of sepsis was applied, established by intraperitoneally LPS injection 3 days after cecal ligation puncture (CLP-LPS)...
May 2, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29686383/the-il-33-pin1-irak-m-axis-is-critical-for-type-2-immunity-in-il-33-induced-allergic-airway-inflammation
#3
Morris Nechama, Jeahoo Kwon, Shuo Wei, Adrian Tun Kyi, Robert S Welner, Iddo Z Ben-Dov, Mohamed S Arredouani, John M Asara, Chun-Hau Chen, Cheng-Yu Tsai, Kyle F Nelson, Koichi S Kobayashi, Elliot Israel, Xiao Zhen Zhou, Linda K Nicholson, Kun Ping Lu
Interleukin 33 (IL-33) is among the earliest-released cytokines in response to allergens that orchestrate type 2 immunity. The prolyl cis-trans isomerase PIN1 is known to induce cytokines for eosinophil survival and activation by stabilizing cytokines mRNAs, but the function of PIN1 in upstream signaling pathways in asthma is unknown. Here we show that interleukin receptor associated kinase M (IRAK-M) is a PIN1 target critical for IL-33 signaling in allergic asthma. NMR analysis and docking simulations suggest that PIN1 might regulate IRAK-M conformation and function in IL-33 signaling...
April 23, 2018: Nature Communications
https://www.readbyqxmd.com/read/29618830/evaluation-of-the-tlr-negative-regulatory-network-in-cvid-patients
#4
Roozbeh Sanaei, Nima Rezaei, Asghar Aghamohammadi, Ali-Akbar Delbandi, Shahram Teimourian, Reza Yazdani, Parsova Tavasolian, Fatemeh Kiaee, Nader Tajik
Common variable immunodeficiency (CVID), a clinically symptomatic primary immunodeficiency disease (PID), is characterized by hypogammaglobulinemia leading to recurrent infections and various complications. Recently, some defects in the signaling of TLRs have been identified in CVID patients which led us to investigate the expression of TLR4 and 9 negative regulatory molecules and their upregulation status following their activation. Using TaqMan real-time PCR, SOCS1, TNFAIP3, RFN216, and IRAK-M transcripts among peripheral blood mononuclear cells (PBMCs) were measured with/without TLR4 and 9 activations...
April 5, 2018: Genes and Immunity
https://www.readbyqxmd.com/read/29434744/interleukin-1-receptor-associated-kinase-3-downregulation-in-peripheral-blood-mononuclear-cells-attenuates-immunosuppression-in-sepsis
#5
Qin Xia, Yupin Zhou, Xi Wang, Shukun Fu
Sepsis is the leading cause of mortality in intensive care units due to complex inflammatory immune responses and immunosuppression. Recent studies have indicated that the negative regulator of toll like receptors, interleukin-1 receptor-associated kinase 3 (IRAK-3/IRAK-M), serves an important role in immunosuppression during sepsis. In the current study, a cecal ligation puncture model was established in mice using lipopolysaccharide secondary challenge to simulate immunosuppression in sepsis. Peripheral blood mononuclear cells (PBMCs) from this model were then used to evaluate the expression and function of IRAK-M...
February 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29144391/antimicrobial-peptide-epinecidin-1-modulates-myd88-protein-levels-via-the-proteasome-degradation-pathway
#6
Bor-Chyuan Su, Jyh-Yih Chen
The cationic antimicrobial peptide epinecidin-1 was identified from Epinephelus coioides and possesses multiple biological functions, including antibacterial, antifungal, anti-tumor, and immunomodulatory effects. In addition, epinecidin-1 suppresses lipopolysaccharide (LPS)-induced inflammation by neutralizing LPS and ameliorating LPS/Toll-like receptor (TLR)-4 internalization. However, it is unclear whether the actions of epinecidin-1 depend on the regulation of TLR adaptor protein MyD88 or endogenous TLR signaling antagonists, which include A20, interleukin-1 receptor associated kinase (IRAK)-M, and suppressor of cytokine signaling (SOCS)-1...
November 16, 2017: Marine Drugs
https://www.readbyqxmd.com/read/29059216/protective-effect-of-dexamethasone-on-5-fu-induced-oral-mucositis-in-hamsters
#7
Susana Barbosa Ribeiro, Aurigena Antunes de Araújo, Raimundo Fernandes de Araújo Júnior, Gerly Anne de Castro Brito, Renata Carvalho Leitão, Maisie Mitchele Barbosa, Vinicius Barreto Garcia, Aldo Cunha Medeiros, Caroline Addison Carvalho Xavier de Medeiros
Oral mucositis (OM) is an important side effect of cancer treatment, characterized by ulcerative lesions in the mucosa of patients undergoing radiotherapy or chemotherapy, which has marked effects on patient quality of life and cancer therapy continuity. Considering that few protocols have demonstrated efficacy in preventing this side effect, the aim of this study was to examine the effect of dexamethasone (DEX) on OM induced by 5-fluorouracil (5-FU) in hamsters by studying signaling pathways. OM was induced in hamsters by 5-FU followed by mechanical trauma (MT) on day 4...
2017: PloS One
https://www.readbyqxmd.com/read/28978688/rab27-dependent-exosome-production-inhibits-chronic-inflammation-and-enables-acute-responses-to-inflammatory-stimuli
#8
COMPARATIVE STUDY
Margaret Alexander, Andrew G Ramstead, Kaylyn M Bauer, Soh-Hyun Lee, Marah C Runtsch, Jared Wallace, Thomas B Huffaker, Dane K Larsen, Tanya Tolmachova, Miguel C Seabra, June L Round, Diane M Ward, Ryan M O'Connell
Extracellular vesicles, including exosomes, have recently been implicated as novel mediators of immune cell communication in mammals. However, roles for endogenously produced exosomes in regulating immune cell functions in vivo are just beginning to be identified. In this article, we demonstrate that Rab27a and Rab27b double-knockout (Rab27DKO) mice that are deficient in exosome secretion have a chronic, low-grade inflammatory phenotype characterized by elevated inflammatory cytokines and myeloproliferation...
November 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28954388/pretreatment-of-pam3csk4-attenuates-inflammatory-responses-caused-by-systemic-infection-of-methicillin-resistant-staphylococcus-aureus-in-mice
#9
Zhaoxia Huang, Xiayu Yi, Yiguo Chen, Xiaorui Hou, Xiangyu Wang, Ping Zhu, Kangmin Zhao, Shuangshuang Wu, Ning Fu, Beiyi Liu
Pam3CSK4 is a synthetic tripalmitoylated lipopeptide that acts as a ligand of TLR1/TLR2 by mimicking the acetylated amino terminus of bacterial lipoproteins. Here we found that pretreatment of Pam3CSK4 protected mice from systemic infection of methicillin-resistant Staphylococcus aureus (MRSA), and enhanced the bacterial clearance in bacteremia model. Pro-inflammatory cytokines, such as TNF-α, IL-6, MCP-1 and IFN-γ were significantly decreased in serum from Pam3CSK4-treated mice. Besides, upon PamCSK4 treatment, the TLR2 expression was down-regulated, IRAK1 phosphorylation was inhibited, and the expression of IRAK-M and Tollip, two negative regulators of NF-κB pathway, was up-regulated...
November 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28951634/effect-of-irak-m-on-airway-inflammation-induced-by-cigarette-smoking
#10
Haihong Gong, Tao Liu, Wei Chen, Weixun Zhou, Jinming Gao
BACKGROUND: IRAK-M, negatively regulating Toll-like receptor, is shown the dual properties in the varied disease contexts. We studied the effect of IRAK-M deficiency on cigarette smoking- (CS-) induced airway inflammation under acute or subacute conditions in a mouse model. METHODS: A number of cellular and molecular techniques were used to detect the differences between IRAK-M knockout (KO) and wild type (WT) mice exposed to 3-day or 7-week CS. RESULTS: Airway inflammation was comparable between IRAK-M KO and WT mice under 3-day CS exposure...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28844953/how-the-biliary-tree-maintains-immune-tolerance
#11
REVIEW
Haiyan Zhang, Patrick S C Leung, M Eric Gershwin, Xiong Ma
The liver is a vital organ with distinctive anatomy, histology and heterogeneous cell populations. These characteristics are of particular importance in maintaining immune homeostasis within the liver microenvironments, notably the biliary tree. Cholangiocytes are the first line of defense of the biliary tree against foreign substances, and are equipped to participate through various immunological pathways. Indeed, cholangiocytes protect against pathogens by TLRs-related signaling; maintain tolerance by expression of IRAK-M and PPARγ; limit immune response by inducing apoptosis of leukocytes; present antigen by expressing human leukocyte antigen molecules and costimulatory molecules; recruit leukocytes to the target site by expressing cytokines and chemokines...
April 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28835201/irak-m-alters-the-polarity-of-macrophages-to-facilitate-the-survival-of-mycobacterium-tuberculosis
#12
Pei Shen, Quan Li, Jilei Ma, Maopeng Tian, Fei Hong, Xinjie Zhai, Jianrong Li, Hanju Huang, Chunwei Shi
BACKGROUND: Intracellular bacterium, Mycobacterium tuberculosis (M. tb), infects specifically macrophages as host cells. IRAK-M, a member of IRAK family, is a negative regulator in TLR signaling and specifically expresses in monocytes and macrophages. The role of IRAK-M in intracellular growth of M. tb and macrophage polarization was explored, for deeply understanding the pathogenesis of M. tb, the significance of IRAK-M to innate immunity and pathogen-host interaction. METHODS: IRAK-M expression was detected in M...
August 23, 2017: BMC Microbiology
https://www.readbyqxmd.com/read/28783585/downregulated-nlrp3-and-nlrp1-inflammasomes-signaling-pathways-in-the-development-and-progression-of-type-1-diabetes-mellitus
#13
Huawei Liu, Ruiying Xu, Qingyu Kong, Jiling Liu, Zhen Yu, Cuifen Zhao
BACKGROUND: NLRP3 and NLRP1 inflammasomes signaling pathways may play an important role in the development and progression of type 1 diabetes mellitus (T1DM). However, relative research is rare. METHODS: The blood mononuclear cells (PBMCs) and granulocytes (GCs) were collected from T1DM patients. The mRNA and protein expression levels were detected by qRT-PCR and Western blotting, respectively. The NLRP3/NLRP1was knocked down by transfected with siRNA, or ovexpressed by infected with lentiviral vectors in PBMCs and GCs from non obese diabetic (NOD) mice, respectively...
October 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28701510/immunomodulatory-molecule-irak-m-balances-macrophage-polarization-and-determines-macrophage-responses-during-renal-fibrosis
#14
Stefanie Steiger, Santhosh V Kumar, Mohsen Honarpisheh, Georg Lorenz, Roman Günthner, Simone Romoli, Regina Gröbmayr, Heni-Eka Susanti, Jan Potempa, Joanna Koziel, Maciej Lech
Activation of various innate immune receptors results in IL-1 receptor-associated kinase (IRAK)-1/IRAK-4-mediated signaling and secretion of proinflammatory cytokines such as IL-12, IL-6, or TNF-α, all of which are implicated in tissue injury and elevated during tissue remodeling processes. IRAK-M, also known as IRAK-3, is an inhibitor of proinflammatory cytokine and chemokine expression in intrarenal macrophages. Innate immune activation contributes to both acute kidney injury and tissue remodeling that is associated with chronic kidney disease (CKD)...
August 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28665693/critical-role-of-irak-m-in-regulating-antigen-induced-airway-inflammation
#15
Mingqiang Zhang, Wei Chen, Weixun Zhou, Yan Bai, Jinming Gao
Asthma is an airway epithelium disorder involving allergic lung inflammation. IL-1 receptor-associated kinase M (IRAK-M) is a negative regulator of Toll-like receptor (TLR) signaling on airway epithelial cells and macrophages, and it is known to limit the overproduction of cytokines during the inflammatory process. However, the direct role of IRAK-M in asthma pathogenesis is unclear. In the present study, we found a significant elevation of IRAK-M expression in mouse lungs after ovalbumin (OVA) exposure. Compared with wild-type mice, IRAK-M knockout (KO) mice responded to OVA challenge with significantly worse infiltration of airway inflammatory cells, greater airway responsiveness, higher proinflammatory cytokine levels in lung homogenates, and more prominent T-helper cell type 2 (Th2) and Th17 deviation...
November 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28609207/protection-of-lipopolysaccharide-lps-preconditioning-against-endotoxin-induced-uveitis-eiu-in-rats-is-associated-with-overexpression-of-interleukin-1-receptor-associated-kinase-m-irak-m
#16
Shuo Yu, Xinli Liu, Nan Zhang, Shuo Yang, Cui Mao, Shilan Feng, Hong Lu
PURPOSE: To investigate the protective effect of LPS preconditioning against EIU in rats. METHODS: EIU in Wistar rats was developed by subcutaneous injection of LPS (200 μg). Lower dose of LPS (0.1 mg/kg, intraperitoneally) or its carrier was injected daily for five days before EIU induction. Twenty-four hours after EIU, eyes were examined and then enucleated. The degree of inflammatory reaction was determined by routine histological examinations. Real-time RT-PCR and Western blot were used to determine the activation of NF-kB and expression of IRAK-1, IRAK-4, and IRAK-M Results: Repeated pre-administration of LPS induced a significant reduction in ocular inflammation and the expression of NF-κb p65 in neurons...
June 13, 2017: Ocular Immunology and Inflammation
https://www.readbyqxmd.com/read/28584078/alcohol-induced-mir-155-and-hdac11-inhibit-negative-regulators-of-the-tlr4-pathway-and-lead-to-increased-lps-responsiveness-of-kupffer-cells-in-alcoholic-liver-disease
#17
Shashi Bala, Timea Csak, Karen Kodys, Donna Catalano, Aditya Ambade, Istvan Furi, Patrick Lowe, Yeonhee Cho, Arvin Iracheta-Vellve, Gyongyi Szabo
Inflammation promotes the progression of alcoholic liver disease. Alcohol sensitizes KCs to gut-derived endotoxin (LPS); however, signaling pathways that perpetuate inflammation in alcoholic liver disease are only partially understood. We found that chronic alcohol feeding in mice induced miR-155, an inflammatory miRNA in isolated KCs. We hypothesized that miR-155 might increase the responsiveness of KCs to LPS via targeting the negative regulators of LPS signaling. Our results revealed that KCs that were isolated from alcohol-fed mice showed a decrease in IRAK-M, SHIP1, and PU...
August 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28432060/toll-like-receptor-2-dominance-over-toll-like-receptor-4-in-stressful-conditions-for-its-detrimental-role-in-the-heart
#18
Ashim K Bagchi, Gauri Akolkar, Soma Mandal, Prathapan Ayyappan, Xi Yang, Pawan K Singal
It has been suggested that Toll-like receptor (TLR)4 promotes IL-10-mediated cardiac cell survival, whereas another receptor, TLR2, from the same family, is detrimental. Here, we examined the interactive role of these two innate signaling molecules under stressful conditions, including IL-10 knockout (IL-10(-/-)) mice, global ischemia-reperfusion (I/R) injury in rat hearts, and in vitro short hairpin RNA experimental models in the presence or absence of IL-10 (10 ng/ml). Circulating and myocardial levels of TNF-α as well as apoptosis and fibrosis were higher in IL-10(-/-) mice...
June 1, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28295231/deficiency-in-irak4-activity-attenuates-manifestations-of-murine-lupus
#19
Michael Murphy, Goutham Pattabiraman, Tissa T Manavalan, Andrei E Medvedev
Interleukin-1 receptor-associated kinase (IRAK) 4 mediates host defense against infections. As an active kinase, IRAK4 elicits full spectra of myeloid differentiation primary response protein (MyD) 88-dependent responses, while kinase-inactive IRAK4 induces a subset of cytokines and negative regulators whose expression is not regulated by mRNA stability. IRAK4 kinase activity is critical for resistance against Streptococcus pneumoniae, but its involvement in autoimmunity is incompletely understood. In this study, we determined the role of IRAK4 kinase activity in murine lupus...
May 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28213090/glycyrrhetinic-acid-attenuates-lipopolysaccharide-induced-fulminant-hepatic-failure-in-d-galactosamine-sensitized-mice-by-up-regulating-expression-of-interleukin-1-receptor-associated-kinase-m
#20
Xinru Yin, Xia Gong, Li Zhang, Rong Jiang, Ge Kuang, Bin Wang, Xinyu Chen, Jingyuan Wan
Glycyrrhetinic acid (GA), the main active ingredient of licorice, reportedly has anti-inflammatory and hepatoprotective properties, but its molecular mechanisms remain be elusive. In the present study, Balb/c mice were pretreated with GA (10, 30, or 100mg/kg) 1h before lipopolysaccharide (LPS)/d-galactosamine (D-GalN) administration. In other in vitro experiment, RAW264.7 macrophages were pretreated with GA before LPS exposure. The mortality, hepatic tissue histology, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were analyzed...
April 1, 2017: Toxicology and Applied Pharmacology
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