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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
#1
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
#2
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
#3
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
#4
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 12, 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
#5
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 4, 2017: GeroScience
https://www.readbyqxmd.com/read/28358285/external-apical-root-resorption-concurrent-with-orthodontic-forces-the-genetic-influence
#6
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
#7
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
#8
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...
January 24, 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
#9
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
#10
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
https://www.readbyqxmd.com/read/28297724/intraocular-delivery-of-mir-146-inhibits-diabetes-induced-retinal-functional-defects-in-diabetic-rat-model
#11
Pei Zhuang, Chithra K Muraleedharan, Shunbin Xu
Purpose: Previously, we showed that microRNA-146 (miR-146) is a pivotal negative feedback regulator of multiple nuclear factor kappa-B (NF-κB) activation pathways in retinal endothelial cells (RECs). We hypothesized that miR-146 plays an important role in diabetic retinopathy (DR) by inhibiting diabetes-induced inflammatory response in the retina. The purpose of the current study is to test this hypothesis in vivo. Methods: Lentiviruses expressing rno-miR-146a, lenti-miR-146a, and negative control oligonucleotide with scrambled sequence, lenti-miR-neg ctl, were produced...
March 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28296893/hnrnp-i-regulates-neonatal-immune-adaptation-and-prevents-colitis-and-colorectal-cancer
#12
Zhigang Jin, Feng Liang, Jing Yang, Wenyan Mei
The intestinal epithelium plays a critical role in host-microbe homeostasis by sensing gut microbes and subsequently initiating proper immune responses. During the neonatal stage, the intestinal epithelium is under immune repression, allowing the transition for newborns from a relatively sterile intra-uterine environment to one that is rich in foreign antigens. The mechanism underlying such immune repression remains largely unclear, but involves downregulation of IRAK1 (interleukin-1 receptor-associated kinase), an essential component of toll-like receptor-mediated NF-κB signaling...
March 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28295231/deficiency-in-irak4-activity-attenuates-manifestations-of-murine-lupus
#13
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...
March 10, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28294689/genomics-signaling-and-treatment-of-waldenstr%C3%A3-m-macroglobulinemia
#14
Zachary R Hunter, Guang Yang, Lian Xu, Xia Liu, Jorge J Castillo, Steven P Treon
Next-generation sequencing has revealed recurring somatic mutations in Waldenström macroglobulinemia (WM). Commonly recurring mutations include MYD88 (95% to 97%), CXCR4 (30% to 40%), ARID1A (17%), and CD79B (8% to 15%). Diagnostic discrimination of WM from overlapping B-cell malignancies is aided by MYD88 mutation status. Transcription is affected by MYD88 and CXCR4 mutations and includes overexpression of genes involved in VDJ recombination, CXCR4 pathway signaling, and BCL2 family members. Among patients with MYD88 mutations, those with CXCR4 mutations show transcriptional silencing of tumor suppressors associated with acquisition of mutated MYD88...
February 13, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28288804/mir-146a-potentially-promotes-ivig-mediated-inhibition-of-tlr4-signaling-in-lps-activated-human-monocytes
#15
Lionel Loubaki, Dominique Chabot, Isabelle Paré, Mathieu Drouin, Renée Bazin
IVIg is used as an immunomodulatory agent in inflammatory disorders such as sepsis. IVIg also affects monocyte differentiation and functions, two processes in which microRNAs play a crucial role. Monocytes detect microorganisms through pathogen recognition receptors (PRRs) such as TLR4. MiR-146a has been shown to supress NF-κB and IRF3 activity, two key components of TLR4 signaling. To evaluate whether miR-146a is involved in the anti-inflammatory effects of IVIg, monocytes were treated with LPS or IVIg alone or, alternately, first activated with LPS followed by washing and addition of IVIg...
March 10, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28279663/mir-146a-mediates-inflammatory-changes-and-fibrosis-in-the-heart-in-diabetes
#16
Biao Feng, Shali Chen, Andrew Devon Gordon, Subrata Chakrabarti
Hyperglycemia induced endothelial injury is a key pathogenetic factor in diabetic cardiomyopathy. In diabetes, changes in pro-inflammatory cytokines are a key mechanism leading to cardiac fibrosis. We have previously demonstrated alteration of miR-146a in chronic diabetic complications. Here, we investigated the role of endothelial miR-146a in mediating inflammation and fibrosis in diabetic cardiomyopathy. To examine the effects of miR-146a on the inflammatory mediators, an endothelial specific miR-146a overexpressing transgenic mice (TG) using tie-2 promoter, was generated...
March 6, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28275790/-mir-142-3p-inhibits-lipopolysaccharide-induced-inflammatory-response-in-human-periodontal-ligament-cells-through-targeting-irak1
#17
Hai-Yan Hu, Jun-Qiang Wang
PURPOSE: To investigate the effects of miR-142-3p overexpression on secretion of inflammatory factors in human periodontal ligament cells (hPDLCs) induced by lipopolysaccharide (LPS) and its underlying mechanism. METHODS: hPDLCs were cultured by tissue cultivation in vitro and treated with various concentrations of LPS for 6, 12, 24 and 48 h. hPDLCs were treated with miR-142-3p mimics for 24 h in the presence of 2.0 μg/mL LPS and the expression levels of inflammatory factors (TNF-α, IL-6 and IL-1β) were detected by ELISA assay...
December 2016: Shanghai Kou Qiang Yi Xue, Shanghai Journal of Stomatology
https://www.readbyqxmd.com/read/28271077/tmem187-irak1-polymorphisms-associated-with-rheumatoid-arthritis-susceptibility-in-tunisian-and-french-female-populations-influence-of-geographic-origin
#18
Olfa Khalifa, Nathalie Balandraud, Nathalie Lambert, Isabelle Auger, Jean Roudier, Audrey Sénéchal, David Geneviève, Christophe Picard, Gérard Lefranc, Isabelle Touitou, Bakridine M'Madi Mrenda, Cécilia Benedito, Etienne Pardoux, Anne-Laure Gagez, Yves-Marie Pers, Christian Jorgensen, Touhami Mahjoub, Florence Apparailly
Polymorphisms have been identified in the Xq28 locus as risk loci for rheumatoid arthritis (RA). Here, we investigated the association between three polymorphisms in the Xq28 region containing TMEM187 and IRAK1 (rs13397, rs1059703, and rs1059702) in two unstudied populations: Tunisian and French. The rs13397 G and rs1059703 T major alleles were significantly increased in RA patients (n = 408) compared with age-matched controls (n = 471) in both Tunisian and French women. These results were confirmed by a meta-analysis replication study including two independent Greek and Korean cohorts...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28237816/mir-146a-promotes-remyelination-in-a-cuprizone-model-of-demyelinating-injury
#19
Jing Zhang, Zheng Gang Zhang, Mei Lu, Xinli Wang, Xia Shang, Stanton B Elias, Michael Chopp
The death of mature oligodendrocytes (OLs) which are the sole myelinating cells of the central nervous system (CNS), leads to demyelination and functional deficits. Currently, there is lack of effective remyelination therapies for patients with demyelinating diseases. MicroRNAs (miRNAs) mediate OL function. We hypothesized that miR-146a, by inactivating interleukin-1 receptor-associated kinase 1 (IRAK1), promotes differentiation of oligodendrocyte progenitor cells (OPCs) and thereby enhances remyelination. To test this hypothesis, a demyelination model induced by a cuprizone (CPZ) diet was employed, in which C57BL/6J mice were fed with a CPZ diet for 5weeks...
February 23, 2017: Neuroscience
https://www.readbyqxmd.com/read/28216638/thymoquinone-an-irak1-inhibitor-with-in-vivo-and-in-vitro-anti-inflammatory-activities
#20
Muhammad Jahangir Hossen, Woo Seok Yang, Daewon Kim, Adithan Aravinthan, Jong-Hoon Kim, Jae Youl Cho
Thymoquinone (TQ) is a bioactive component of black seed (Nigella sativa) volatile oil and has been shown to have anti-oxidative, anti-inflammatory, and anti-cancer properties. In the present study, we explored the molecular mechanisms that underlie the anti-inflammatory effect of TQ and its target proteins using lipopolysaccharide (LPS)-stimulated murine macrophage-like RAW264.7 and human monocyte-like U937 cells, together with LPS/D-galactosamine (GalN)-induced acute hepatitis and HCl/EtOH-induced gastritis mouse models...
February 20, 2017: Scientific Reports
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