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https://www.readbyqxmd.com/read/28536249/bronchial-inflammation-and-bacterial-load-in-stable-copd-is-associated-with-tlr4-overexpression
#1
Antonino Di Stefano, Fabio L M Ricciardolo, Gaetano Caramori, Ian M Adcock, Kian Fan Chung, Peter J Barnes, Paola Brun, Andrea Leonardi, Filippo Andò, Davide Vallese, Isabella Gnemmi, Luisella Righi, Francesco Cappello, Bruno Balbi
Toll-like receptors (TLRs) and nucleotide-binding oligomerisation domain (NOD)-like receptors (NLRs) are two major forms of innate immune sensors but their role in the immunopathology of stable chronic obstructive pulmonary disease (COPD) is incompletely studied. Our objective here was to investigate TLR and NLR signalling pathways in the bronchial mucosa in stable COPD.Using immunohistochemistry, the expression levels of TLR2, TLR4, TLR9, NOD1, NOD2, CD14, myeloid differentiation primary response gene 88 (MyD88), Toll-interleukin-1 receptor domain-containing adaptor protein (TIRAP), and the interleukin-1 receptor-associated kinases phospho-IRAK1 and IRAK4 were measured in the bronchial mucosa of subjects with stable COPD of different severity (n=34), control smokers (n=12) and nonsmokers (n=12)...
May 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28512203/the-mechanism-of-activation-of-irak1-and-irak4-by-interleukin-1-and-toll-like-receptor-agonists
#2
Stefan Vollmer, Sam Strickson, Tinghu Zhang, Nathanael Gray, Katherine Lee, Vikram Rao, Philip Cohen
We have developed the first assays that measure the protein kinase activities of Interleukin-1 Receptor Associated Kinase 1 (IRAK1) and IRAK4 reliably in human cell extracts, by employing Pellino1 as a substrate in conjunction with specific pharmacological inhibitors of IRAK1 and IRAK4. We exploited these assays to show that IRAK4 was constitutively active and that its intrinsic activity towards Pellino1 was not increased significantly by stimulation with interleukin-1 (IL-1) in IL-1R-expressing HEK293 cells, Pam3Csk4-stimulated human THP1 monocytes or primary human macrophages...
May 16, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28506791/enterovirus-71-induced-has-mir-21-contributes-to-evasion-of-host-immune-system-by-targeting-myd88-and-irak1
#3
Na Feng, Zhizhao Zhou, Yuanxia Li, Lifang Zhao, Zhengfeng Xue, Rong Lu, Kunpeng Jia
Enterovirus71(EV71), the etiological agent of hand-foot-and-mouth disease, has increasingly become a public health challenge around the world. Type I interferons (IFNs) are an important family of cytokines that regulate innate and adaptive immune responses to pathogens.These pathways are tightly regulated by the host to prevent an inappropriate cellular response, but viruses can modulate these pathways to proliferate and spread. In this study, we demonstrated that EV71 evades the immune surveillance system to proliferate by activating microRNA-21...
May 12, 2017: Virus Research
https://www.readbyqxmd.com/read/28504607/innate-inflammatory-gene-expression-profiling-in-potential-brain-dead-donors-detailed-investigation-of-the-effect-of-common-corticosteroid-therapy
#4
Reza Gholamnezhadjafari, Nader Tajik, Reza Falak, Reza Aflatoonian, Sanaz Dehghan, Abbas Rezaei
Our study aimed to assess the influence of common methylprednisolone therapy on innate inflammatory factors in potential brain-dead organ donors (BDDs). The study groups consisted of 50 potential BDDs who received 15 mg/kg/d methylprednisolone and 25 live organ donors (LDs) as control group. Innate immunity gene expression profiling was performed by RT-PCR array. Soluble serum cytokines and chemokines, complement components, heat shock protein 70 (HSP70) and high mobility group box-1 (HMGB1) were measured by ELISA...
January 1, 2017: Innate Immunity
https://www.readbyqxmd.com/read/28486961/role-of-heparin-in-pulmonary-cell-populations-in-an-in-vitro-model-of-acute-lung-injury
#5
Marta Camprubí-Rimblas, Raquel Guillamat-Prats, Thomas Lebouvier, Josep Bringué, Laura Chimenti, Manuela Iglesias, Carme Obiols, Jessica Tijero, Lluís Blanch, Antonio Artigas
BACKGROUND: In the early stages of acute respiratory distress syndrome (ARDS), pro-inflammatory mediators inhibit natural anticoagulant factors and initiate an increase in procoagulant activity. Previous studies proved the beneficial effects of heparin in pulmonary coagulopathy, which derive from its anticoagulant and anti-inflammatory activities, although it is uncertain whether heparin works. Understanding the specific effect of unfractioned heparin on cell lung populations would be of interest to increase our knowledge about heparin pathways and to treat ARDS...
May 10, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28475177/the-role-of-hybrid-ubiquitin-chains-in-the-myd88-and-other-innate-immune-signalling-pathways
#6
REVIEW
Philip Cohen, Sam Strickson
The adaptor protein MyD88 is required for signal transmission by toll-like receptors and receptors of the interleukin-1 family of cytokines. MyD88 signalling triggers the formation of Lys63-linked and Met1-linked ubiquitin (K63-Ub, M1-Ub) chains within minutes. The K63-Ub chains, which are formed by the E3 ubiquitin ligases TRAF6, Pellino1 and Pellino2, activate TAK1, the master kinase that switches on mitogen-activated protein (MAP) kinase cascades and initiates activation of the canonical IκB kinase (IKK) complex...
May 5, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28470929/down-regulation-of-increased-traf6-expression-in-the-peripheral-mononuclear-cells-of-patients-with-primary-sj%C3%A3-gren-s-syndrome-by-an-ebv-eber1-specific-synthetic-single-stranded-complementary-dna-molecule
#7
Sándor Sipka, Erika Zilahi, Gábor Papp, Ji-Qing Chen, Andrea Nagy, Katalin Hegyi, József Kónya, Margit Zeher
AIM: We described earlier a simultaneously increased that the increased expression of miRNA-146a/b was accompanied by an increase in the expression of and TRAF6 and a decrease in the expression of IRAK1 genes in the peripheral mononuclear cells (PBMCs) of patients with primary Sjogren's syndrome (pSS) patients. Recently, the expression of EBV encoded. RNA (EBER) was published in the B cells of salivary glands of in pSS. In the present study, we applied an EBV-EBER1 specific synthetic single stranded complementary DNA molecule (EBV-EBER1-cDNA) to test whether any EBER1 related effect exists also in PBMCs of pSS patients...
May 3, 2017: International Journal of Rheumatic Diseases
https://www.readbyqxmd.com/read/28465253/anti-inflammatory-action-of-2-carbomethoxy-2-3-epoxy-3-prenyl-1-4-naphthoquinone-cmep-nq-suppresses-both-the-myd88-dependent-and-trif-dependent-pathways-of-tlr4-signaling-in-lps-stimulated-raw264-7-cells
#8
Hyun Ju Woo, Do Youn Jun, Ji Young Lee, Hae Sun Park, Mi Hee Woo, Sook Jahr Park, Sang Chan Kim, Chae Ha Yang, Young Ho Kim
ETHNOPHARMACOLOGICAL RELEVANCE: The roots of Rubia cordifolia L. have been widely used as a traditional herbal medicine in Northeast Asia for treatment of inflammatory diseases. AIM OF THE STUDY: To elucidate the anti-inflammatory mechanism of 2-carbomethoxy-2,3-epoxy-3- prenyl-1,4-naphthoquinone (CMEP-NQ), purified from the roots of R. cordifolia L. as the major anti-inflammatory component, in LPS-treated RAW264.7 murine macrophage cells. MATERIALS AND METHODS: Anti-inflammatory activity of CMEP-NQ was investigated in LPS-treated RAW264...
April 29, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28456576/influence-of-the-total-saponin-fraction-from-dioscorea-nipponica-makino-on-tlr2-4-il1r-receptor-singnal-pathway-in-rats-of-gouty-arthritis
#9
Qi Zhou, Fang Fang Lin, Shu Min Liu, Xiao Fang Sui
ETHNOPHARMACOLOGICAL RELEVANCE: Dioscorea nipponica Makino have been extensively used in traditional medicine for the treatment of arthritic diseases, particularly gouty arthritis (GA). MATERIALS AND METHODS: Sixty male Wistar rats were divided into six groups: the normal group, model group, colchicine group (COL) and three total saponin groups (RDN) (high dose [160 mg/kg], middle dose [80 mg/kg] and low dose [40 mg/kg]). The mRNA and protein expression levels of TLR2, TLR4, IRAK1, TRAF6, TAK1, IKKα, IκBα and NF-κB in the synovial tissue of joint were detected by realtime PCR and WB methods respetively...
April 26, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28451396/association-between-interleukin-1-receptor-associated-kinase-1-rs3027898-a-c-gene-polymorphism-and-rheumatoid-arthritis
#10
Mahdi Atabaki, Mohammad Hashemi, Hamid Daneshvar, Ebrahim Alijani
Rheumatoid arthritis (RA) is a systemic autoimmune disease predominantly involving the synovial joints and affects up to 1% of adults worldwide. The aim of the present study was to determine whether the interleukin-1 receptor (IL1R)-associated kinase (IRAK1) rs3027898 gene polymorphism confers susceptibility to RA in a sample of patients from Iran. This gene encodes IRAK1, one of two putative serine/threonine kinases that associates with IL1R upon stimulation. IRAK1 is partially responsible for IL-1-induced upregulation of the transcription factor, nuclear factor-κB...
March 2017: Biomedical Reports
https://www.readbyqxmd.com/read/28440395/microrna-mediated-inflammatory-responses-induced-by-cryptococcus-neoformans-are-dependent-on-the-nf-%C3%AE%C2%BAb-pathway-in-human-monocytes
#11
Hong Chen, Yi Jin, Huan Chen, Ningxin Liao, Yan Wang, Jianghan Chen
Cryptococcosis is a significant invasive fungal infection with noteworthy morbidity and mortality that is usually caused by either Cryptococcus neoformans (C. neoformans) or Cryptococcus gattii (C. gattii). Epidemiological studies have indicated that C. neoformans are more often reported in immunocompromised and immunocompetent patients. It has been well established that the cytokine profile of the host markedly affects the outcome of cryptococcal disease, and the negative regulators of microRNAs(miRs or miRNAs) are critically important for immunomodulation...
April 12, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28434122/the-status-of-pulmonary-fibrosis-in-systemic-sclerosis-is-associated-with-irf5-stat4-irak1-and-ctgf-polymorphisms
#12
Wenjie Zhao, Xiaoyang Yue, Kuai Liu, Junfeng Zheng, Runda Huang, Jun Zou, Gabriela Riemekasten, Frank Petersen, Xinhua Yu
Pulmonary fibrosis (PF) is one of the leading causes of death in systemic sclerosis (SSc) patients. Although all SSc patients are characterized by autoimmunity, only part of them suffer from PF, suggesting that beside autoimmunity, some additional factors are involved in the initiation of PF in SSc. In this study, we aimed to identify genetic polymorphisms associated with the status of PF in SSc. We performed that an exhaustive search of the PubMed database was performed to identify eligible studies. Then, a comprehensive meta-analysis was performed by comparing PF(+)-SSc and PF(-)-SSc patients to identify genetic polymorphisms associated with the status of PF in SSc...
April 22, 2017: Rheumatology International
https://www.readbyqxmd.com/read/28431280/interleukin-1-receptor-associated-kinase-1-is-a-potential-therapeutic-target-of-anti-inflammatory-therapy-for-systemic-lupus-erythematosus
#13
Mingfang Li, Datang Yu, Bing Ni, Fei Hao
Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease and currently has no effective therapy. The genome-wide analyses indicate that interleukin-1 receptor associated kinase 1 (IRAK1) is associated with the susceptibility of SLE in humans. In the present study, we identified that IRAK1 was overexpressed and hyper-activated in splenic mononuclear cells from B6.MRL-Fas(lpr)/Nju (B6.lpr) mice and peripheral blood mononuclear cells (PBMCs) from SLE patients. Intraperitoneal treatment with a small molecular inhibitor of IRAK1 (IRAK1/4 inhibitor or IRAK-Inh) significantly mitigated inflammatory responses and renal injury in B6...
April 18, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28404732/roles-of-the-traf6-and-pellino-e3-ligases-in-myd88-and-rankl-signaling
#14
Sam Strickson, Christoph H Emmerich, Eddy T H Goh, Jiazhen Zhang, Ian R Kelsall, Thomas Macartney, C James Hastie, Axel Knebel, Mark Peggie, Francesco Marchesi, J Simon C Arthur, Philip Cohen
It is widely accepted that the essential role of TRAF6 in vivo is to generate the Lys63-linked ubiquitin (K63-Ub) chains needed to activate the "master" protein kinase TAK1. Here, we report that TRAF6 E3 ligase activity contributes to but is not essential for the IL-1-dependent formation of K63-Ub chains, TAK1 activation, or IL-8 production in human cells, because Pellino1 and Pellino2 generate the K63-Ub chains required for signaling in cells expressing E3 ligase-inactive TRAF6 mutants. The IL-1-induced formation of K63-Ub chains and ubiquitylation of IRAK1, IRAK4, and MyD88 was abolished in TRAF6/Pellino1/Pellino2 triple-knockout (KO) cells, but not in TRAF6 KO or Pellino1/2 double-KO cells...
April 25, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28378188/apigenin-suppresses-the-senescence-associated-secretory-phenotype-and-paracrine-effects-on-breast-cancer-cells
#15
Kevin M Perrott, Christopher D Wiley, Pierre-Yves Desprez, Judith Campisi
Apigenin (4',5,7,-trihydroxyflavone) is a flavonoid found in certain herbs, fruits, and vegetables. Apigenin can attenuate inflammation, which is associated with many chronic diseases of aging. Senescent cells-stressed cells that accumulate with age in mammals-display a pro-inflammatory senescence-associated secretory phenotype (SASP) that can drive or exacerbate several age-related pathologies, including cancer. Flavonoids, including apigenin, were recently shown to reduce the SASP of a human fibroblast strain induced to senesce by bleomycin...
April 2017: GeroScience
https://www.readbyqxmd.com/read/28358285/external-apical-root-resorption-concurrent-with-orthodontic-forces-the-genetic-influence
#16
Nuria Nieto-Nieto, Jose Enrique Solano, Rosa Yañez-Vico
Root resorption is a pathological process of multifactorial origin related to the permanent loss of dental root structure in response to a mechanical, inflammatory, autoimmune or infectious stimulus. External apical root resorption (EARR) is a frequent clinical complication secondary to orthodontic tooth movement; apart from variables related to treatment, environmental factors and/or interindividual genetic variations can confer susceptibility or resistance to its occurrence. In this context, genetic predisposition has been described as an etiological factor, together with mechanical factors derived from orthodontic treatment...
May 2017: Acta Odontologica Scandinavica
https://www.readbyqxmd.com/read/28356759/diagnostic-and-prognostic-roles-of-irak1-in-hepatocellular-carcinoma-tissues-an-analysis-of-immunohistochemistry-and-rna-sequencing-data-from-the-cancer-genome-atlas
#17
Zhi-Hua Ye, Li Gao, Dong-Yue Wen, Yun He, Yu-Yan Pang, Gang Chen
BACKGROUND: IRAK1 has been repoted to play an essential role in the development of multiple cancers. However, the clinical significance of IRAK1 in hepatocellular carcinoma (HCC) and the underlying molecular mechanism remain unclear. Therefore, we aimed to investigate the role of IRAK1 in the pathogenesis of HCC in this study. MATERIALS AND METHODS: HCC tissues and para-carcinoma tissues were collected for immunohistochemistry (IHC) analysis to evaluate IRAK1 expression...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28324845/pharmacological-effects-of-%C3%AE-d-mannuronic-acid-m2000-on-mir-146a-irak1-traf6-and-nf-%C3%AE%C2%BAb-gene-expression-as-target-molecules-in-inflammatory-reactions
#18
Seyed Shahabeddin Mortazavi Jahromi, Mehdi Malek Jamshidi, Ali Farazmand, Zahra Aghazadeh, Mehdi Yousefi, Abbas Mirshafiey
BACKGROUND: Impaired expression and function of microRNAs (miRNAs) are involved in the pathogenesis of many autoimmune and inflammatory diseases. Moreover, there is a close relationship between TLRs and miRNAs and impairment in regulating their expression which can play a vital role in the immunopathogenesis of many inflammatory reactions. This research aimed to study the pharmaceutical effects of M2000 (β-d-mannuronic acid) on the expression of miR-146a and its two target molecules (IRAK1 and TRAF6), and the transcription factor NF-κB in the HEK-Blue hTLR2 cell line...
June 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28319200/induction-of-immunomodulatory-mir-146a-and-mir-155-in-small-intestinal-epithelium-of-vibrio-cholerae-infected-patients-at-acute-stage-of-cholera
#19
Aziz Bitar, Rituparna De, Silvia Melgar, Kyaw Min Aung, Arman Rahman, Firdausi Qadri, Sun Nyunt Wai, Tahmina Shirin, Marie-Louise Hammarström
The potential immunomodulatory role of microRNAs in small intestine of patients with acute watery diarrhea caused by Vibrio cholerae O1 or enterotoxigenic Escherichia coli (ETEC) infection was investigated. Duodenal biopsies were obtained from study-participants at the acute (day 2) and convalescent (day 21) stages of disease, and from healthy individuals. Levels of miR-146a, miR-155 and miR-375 and target gene (IRAK1, TRAF6, CARD10) and 11 cytokine mRNAs were determined by qRT-PCR. The cellular source of microRNAs in biopsies was analyzed by in situ hybridization...
2017: PloS One
https://www.readbyqxmd.com/read/28302064/a-sibship-with-duplication-of-xq28-inherited-from-the-mother-genomic-characterization-and-clinical-outcomes
#20
Dong Keon Yon, Ji Eun Park, Seung Jun Kim, Sung Han Shim, Kyu Young Chae
BACKGROUND: Loss-of-function mutations in methyl-CpG-binding protein 2 (MECP2; MIM *300005) results in the Rett syndrome, whereas gain-of-function mutations are associated with the MECP2 duplication syndrome. METHODS: We did research on a family with two brothers showing Xq28 duplication syndrome using various molecular cytogenetic techniques such as multiplex ligation-dependent probe amplification and array-based genomic hybridization. RESULTS: The duplicated region had several genes including MECP2 and interleukin-1 receptor associated kinase 1 (IRAK1; MIM *300283)...
March 17, 2017: BMC Medical Genetics
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