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https://www.readbyqxmd.com/read/28077577/extracellular-microrna-signature-of-human-helper-t-cell-subsets-in-health-and-autoimmunity
#1
Anna Torri, Donatella Carpi, Elisabetta Bulgheroni, Maria-Cristina Crosti, Monica Moro, Paola Gruarin, Riccardo L Rossi, Grazisa Rossetti, Dolores Di Vizio, Mirjam Hoxha, Valentina Bollati, Cristina Gagliani, Carlo Tacchetti, Moira Paroni, Jens Geginat, Laura Corti, Luigia Venegoni, Emilio Berti, Massimiliano Pagani, Giuseppe Matarese, Sergio Abrignani, Paola de Candia
Upon TCR stimulation, CD4+ T lymphocytes release extracellular vesicles (EVs) containing microRNAs. However, no data are available on whether human CD4+ T cell subsets release EVs containing different pattern of microRNAs. The present work aimed at filling this gap by assessing the microRNA content in EVs released upon in vitro TCR stimulation of Th1, Th17 and T regulatory (Treg) cells. Our results indicate that EVs released by Treg cells are significantly different compared to those released by the other subsets...
January 11, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28069966/inherited-human-irak-1-deficiency-selectively-impairs-tlr-signaling-in-fibroblasts
#2
Erika Della Mina, Alessandro Borghesi, Hao Zhou, Salim Bougarn, Sabri Boughorbel, Laura Israel, Ilaria Meloni, Maya Chrabieh, Yun Ling, Yuval Itan, Alessandra Renieri, Iolanda Mazzucchelli, Sabrina Basso, Piero Pavone, Raffaele Falsaperla, Roberto Ciccone, Rosa Maria Cerbo, Mauro Stronati, Capucine Picard, Orsetta Zuffardi, Laurent Abel, Damien Chaussabel, Nico Marr, Xiaoxia Li, Jean-Laurent Casanova, Anne Puel
Most members of the Toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) families transduce signals via a canonical pathway involving the MyD88 adapter and the interleukin-1 receptor-associated kinase (IRAK) complex. This complex contains four molecules, including at least two (IRAK-1 and IRAK-4) active kinases. In mice and humans, deficiencies of IRAK-4 or MyD88 abolish most TLR (except for TLR3 and some TLR4) and IL-1R signaling in both leukocytes and fibroblasts. TLR and IL-1R responses are weak but not abolished in mice lacking IRAK-1, whereas the role of IRAK-1 in humans remains unclear...
January 9, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28060792/expression-of-x-linked-toll-like-receptor-4-signalling-genes-in-female-versus-male-neonates
#3
David N O'Driscoll, Chiara DeSanti, Paul J McKiernan, Victoria McEneaney, Eleanor J Molloy, Catherine M Greene
BACKGROUND: Male neonates display poorer disease prognosis and outcomes compared to females. Immune genes which exhibit higher expression in umbilical cord blood (UCB) of females may contribute to the female immune advantage during infection and inflammation. The aim of this study was to quantify expression of Toll-like receptor (TLR) 4 signalling genes encoded on the X-chromosome in UCB from term female versus male neonates. METHODS: UCB samples were collected from term neonates (n=26) born by elective Caesarean section and whole blood was collected from adults (n=20)...
January 6, 2017: Pediatric Research
https://www.readbyqxmd.com/read/27931243/phase-1-2-study-of-pacritinib-a-next-generation-jak2-flt3-inhibitor-in-myelofibrosis-or-other-myeloid-malignancies
#4
Srdan Verstovsek, Olatoyosi Odenike, Jack W Singer, Tanya Granston, Suliman Al-Fayoumi, H Joachim Deeg
BACKGROUND: Pacritinib (SB1518) is a highly selective kinase inhibitor with specificity for JAK2, FLT3, IRAK1, and CFS1R. This multicenter phase 1/2 study evaluated the maximum tolerated dose (MTD), safety, and clinical activity of pacritinib in patients with myelofibrosis (MF) and other advanced myeloid malignancies. METHODS: In the phase 1 dose-escalation part of the study, 43 adults with advanced myeloid malignancies received pacritinib 100 to 600 mg once daily (QD)...
December 8, 2016: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/27922090/mir-146a-mediated-suppression-of-the-inflammatory-response-in-human-adipocytes
#5
Julian Roos, Eveliina Enlund, Jan-Bernd Funcke, Daniel Tews, Karlheinz Holzmann, Klaus-Michael Debatin, Martin Wabitsch, Pamela Fischer-Posovszky
The obesity-associated inflammation of white adipose tissue (WAT) is one of the factors leading to the development of related diseases such as insulin resistance and liver steatosis. Recently, microRNAs (miRNAs) were identified as important regulators of WAT functions. Herein, we cultured human Simpson-Golabi-Behmel syndrome (SGBS) adipocytes with macrophage-conditioned medium (MacCM) and performed an Affimetrix miRNA array to identify miRNAs differentially expressed under inflammatory conditions. We identified 24 miRNAs differentially expressed upon inflammation in human adipocytes and miR-146a was the most up-regulated miRNA species...
December 6, 2016: Scientific Reports
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
#6
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/27883091/mycobacterium-tuberculosis-triggered-hippo-pathway-orchestrates-cxcl1-2-expression-to-modulate-host-immune-responses
#7
Monoranjan Boro, Vikas Singh, Kithiganahalli Narayanaswamy Balaji
Mycobacterium tuberculosis (Mtb) pathogenesis encompasses a plethora of finely regulated alterations within the host which eventually coin the outcome of infection. Chemokines are important components in directing immune cell recruitment to the site of infection, and shaping the disease progression. Here, we demonstrate that Hippo (mammalian sterile 20-like 1 and 2 kinases, MST1/2, in mammals), is activated during mycobacterial infection in a toll-like receptor (TLR) 2-interleukin receptor-1 associated kinases (IRAK1/4)-dependent manner...
November 24, 2016: Scientific Reports
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
#8
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/27864528/irak1-and-irak4-promote-phosphorylation-ubiquitination-and-degradation-of-myd88-adaptor-like-mal
#9
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/27845876/hypoxia-induced-microrna-146a-represses-bcl-2-through-traf6-irak1-but-not-smad4-to-promote-chondrocyte-autophagy
#10
Guanghui Chen, Xin Gao, Jing Wang, Cheng Yang, Yang Wang, Yonggang Liu, Weiwei Zou, Tielong Liu
It has been shown that hypoxia stimulation promotes chondrocytes autophagy partly through HIF-1α, miR-146a and Bcl-2 progressively, and this mechanism represented the connection among hypoxia, miR-146a and autophagy, and provides a possible therapeutic strategy for osteoarthritis. However, the interaction between miR-146a and Bcl-2 is still unclear. Here in a hypoxic environment, we quantified the three reported miR-146a targets: two inflammation related targets Traf6, IRAK1; and the only reported target in chondrocytes Smad4...
December 19, 2016: Biological Chemistry
https://www.readbyqxmd.com/read/27830143/microrna-146a-contributes-to-sci-recovery-via-regulating-traf6-and-irak1-expression
#11
Jinsong Wei, Jiafeng Wang, Yulan Zhou, Shouquan Yan, Keshen Li, Hongsheng Lin
MicroRNA-146a participates in spinal cord injury (SCI) recovery. Until recently, how miRNA-146a participates in SCI remained unclear. In this study, we tried to explore the roles of miRNA-146a in the recovery of SCI using a rat model. The expression of the probable target genes of miRNA-146a (including IRAK1 and TARF6) as well as proinflammation cytokines were measured until 7 days after surgery in the three groups (sham group, SCI group, and miRNA-146a antagomir injection group). Also, the animals' motivations were estimated using Basso Beattie Bresnahan (BBB) during the whole experiment...
2016: BioMed Research International
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
#12
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/27790836/neighboring-phosphoser-pro-motifs-in-the-undefined-domain-of-irak1-impart-bivalent-advantage-for-pin1-binding
#13
Monique J Rogals, Alexander I Greenwood, Jeahoo Kwon, Kun Ping Lu, Linda K Nicholson
The peptidyl prolyl isomerase Pin1 has two domains that are considered to be its binding (WW) and catalytic (PPIase) domains, both of which interact with phosphorylated Ser/Thr-Pro motifs. This shared specificity might influence substrate selection, as many known Pin1 substrates have multiple sequentially close phosphoSer/Thr-Pro motifs, including the protein interleukin-1 receptor-associated kinase-1 (IRAK1). The IRAK1 undefined domain (UD) contains two sets of such neighboring motifs (Ser131/Ser144 and Ser163/Ser173), suggesting possible bivalent interactions with Pin1...
December 2016: FEBS Journal
https://www.readbyqxmd.com/read/27702822/constitutive-irak4-activation-underlies-poor-prognosis-and-chemoresistance-in-pancreatic-ductal-adenocarcinoma
#14
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
#15
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/27664853/iinq-attenuates-systemic-inflammatory-responses-via-selectively-impairing-the-myddosome-complex-formation-upon-tlr4-ligation
#16
Kidong Kang, Minho Won, Jae-Min Yuk, Chan-Yong Park, Hee Sun Byun, Kyeong Ah Park, So-Ra Lee, Young-Goo Kang, Han-Ming Shen, Ill Young Lee, Gang Min Hur
A specific small-molecule inhibitor of the TLR4 signaling complex upstream of the IKK would likely provide therapeutic benefit for NF-κB-mediated inflammatory disease. We previously identified brazilin as a selective upstream IKK inhibitor targeting the Myddosome complex. In this study, using a cell-based ubiquitination assay for IRAK1 and a chemical library comprising a series of structural analogues of brazilin, a novel small molecule, 2-hydroxy-5,6-dihydroisoindolo[1,2-a]isoquinoline-3,8-dione (IinQ), was identified as a selective and potent inhibitor of IRAK1-dependent NF-κB activation upon TLR4 ligation...
September 21, 2016: Biochemical Pharmacology
https://www.readbyqxmd.com/read/27640899/tnfaip3-a-negative-regulator-of-the-tlr-signaling-pathway-is-a-potential-predictive-biomarker-of-response-to-antidepressant-treatment-in-major-depressive-disorder
#17
Yi-Yung Hung, Chin-Chuen Lin, Hong-Yo Kang, Tiao-Lai Huang
Inflammation and abnormalities in Toll-like receptor (TLR) expression and activation have been linked to major depressive disorder (MDD). However, negative regulators of TLR pathways have not been previously investigated in this context. Here, we sought to investigate the association of depression severity, measured by the 17-item Hamilton Depression Rating Scale (HAMD-17), with mRNA expression levels of negative regulators of the TLR pathway, including SOCS1, TOLLIP, SIGIRR, MyD88s, NOD2 and TNFAIP3, in peripheral blood mononuclear cells (PBMCs) from 100 patients with MDD and 53 healthy controls, before and after treatment with antidepressants...
January 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/27636999/toll-like-4-receptor-nf%C3%AE%C2%BAb-inflammatory-mir-146a-pathway-contributes-to-the-art-correlated-preterm-birth-outcome
#18
Xinqi Zhong, Yi-Zhou Jiang, Peiwen Liu, Wenzhi He, Zhongtang Xiong, Weijie Chang, Jiandong Zhu, Qiliang Cui
Assisted reproductive technology (ART) is widely used for the women with infertility conditions to achieve pregnancy. However, the adverse effects of ART may lead to poor perinatal and neonatal outcomes, e.g., preterm birth and low body weight. In this study, we investigated the inflammatory molecular factors and microRNA that might be involved in ART related preterm birth. We found the elevation of Toll-like 4 receptor (TLR4), activation of NFκB pathway and down-regulation of microRNA-146a (miR-146a), a negative regulator of NFκB, in the placenta of preterm birth and ART, indicating preterm birth and ART were associated with inflammation signaling activation...
September 12, 2016: Oncotarget
https://www.readbyqxmd.com/read/27619757/targeting-interleukin-1-receptor-associated-kinase-1-for-human-hepatocellular-carcinoma
#19
Ning Li, Jinhua Jiang, Jing Fu, Ting Yu, Bibo Wang, Wenhao Qin, An Xu, Mengchao Wu, Yao Chen, Hongyang Wang
BACKGROUND: Interleukin-1 receptor associated kinase 1 (IRAK1), as a down-stream of toll-like receptor (TLR) signaling, plays important roles in series of malignancies. However, the role of IRAK1 in hepatocellular carcinoma (HCC) remains little known. METHODS: In our study, reverse transcription-PCR (RT-PCR), Western Blot, and immunohistochemical staining were used to assess the mRNA and protein levels of IRAK1 in clinical samples and cell lines. Cell counting assay and flow cytometry were employed to analyze the effect of IRAK1 on cell cycle and apoptosis...
2016: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/27581002/association-between-irak1-rs3027898-and-mirna-499-rs3746444-polymorphisms-and-rheumatoid-arthritis-a-case-control-study-and-meta-analysis
#20
X-K Yang, P Li, C Zhang, R-X Leng, S Li, J Liu, B-Z Li, H-F Pan, D-Q Ye
BACKGROUND: The IRAK1 and miR-499 polymorphisms play an important role in the etiology of rheumatoid arthritis (RA). Several studies have been carried out to estimate the association between IRAK1 rs3027898 and miR-499 rs3746444 and RA risk; however, the results were inconsistent. AIM: A case control study was carried out to explore the association between IRAK1 rs3027898 and miR-499 rs3746444 and the RA risk in a Chinese population. Meta-analyses combining present with previous studies were conducted to further explore the association...
August 31, 2016: Zeitschrift Für Rheumatologie
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