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https://www.readbyqxmd.com/read/28216638/thymoquinone-an-irak1-inhibitor-with-in-vivo-and-in-vitro-anti-inflammatory-activities
#1
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
https://www.readbyqxmd.com/read/28209713/mir-718-represses-pro-inflammatory-cytokine-production-through-targeting-pten
#2
Parisa Kalantari, Omid F Harandi, Sarika Agarwal, Florentina Rus, Evelyn A Kurt-Jones, Katherine A Fitzgerald, Daniel R Caffrey, Douglas T Golenbock
Bacterial sepsis involves a complex interaction between the host immune response and bacterial lipopolysaccharides (LPS). LPS binds Toll-like receptor (TLR) 4, which leads to the release of pro-inflammatory cytokines that are essential for a potent innate immune response against pathogens. The innate immune system is tightly regulated as excessive inflammation can lead to organ failure and death. MicroRNAs have recently emerged as important regulators of the innate immune system. Here, we determined the function of miR-718, which is conserved across mammals and overlaps with the 5 UTR of the Interleukin-1 Receptor-Associated Kinase (IRAK1) gene...
February 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28207326/micro-rna-146a-but-not-irak1-is-associated-with-rheumatoid-arthritis-in-the-tunisian-population
#3
Hana Ben Hassine, Asma Boumiza, Rim Sghiri, Khadija Baccouche, Imen Boussaid, Ahlem Atig, Zahid Shakoor, Elyes Bouajina, Ramzi Zemni
BACKGROUND: Rheumatoid arthritis (RA) is characterized by the production of an array of proinflammatory cytokines through the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway. Interleukin-1 receptor (IL-1R) and Toll-like receptors contain a common cytoplasmic motif the Toll/IL-1R (TIR) homology domain. This motif is required for NF-κB activation. IL-1R-associated kinase 1 (IRAK1) is a key adapter molecule recruited during the signaling cascade of the TIR...
February 2017: Genetic Testing and Molecular Biomarkers
https://www.readbyqxmd.com/read/28161165/supplemental-methionine-choline-or-taurine-alter-in-vitro-gene-network-expression-of-polymorphonuclear-leukocytes-from-neonatal-holstein-calves
#4
M K Abdelmegeid, M Vailati-Riboni, A Alharti, F Batistel, J J Loor
Isolated PMNL from neonatal calves were used to evaluate the effect of Met, choline, and taurine supplementation on mRNA expression of genes related to the Met cycle and innate immunity. Five neonatal Holstein calves (3 wk old) were used for PMNL isolation and in vitro culture. The selected genes were related to the 1-carbon and Met cycles, cell signaling and cytokine mediators, inflammation, antimicrobial and killing mechanism associated genes, immune mediators, adhesion, and pathogen recognition. The results indicated that supplementation of Met, choline, and taurine increased homocysteine synthesis through upregulation of SAHH...
February 1, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28131813/microrna-146a-induction-during-influenza-h3n2-virus-infection-targets-and-regulates-traf6-levels-in-human-nasal-epithelial-cells-hnecs
#5
Yuqin Deng, Yan Yan, Kai Sen Tan, Jing Liu, Vincent T Chow, Ze-Zhang Tao, De-Yun Wang
We have previously shown that human nasal epithelial cells (hNECs) are highly permissive cells for respiratory viruses including influenza A virus (IAV) and respiratory syncytial virus. Recent studies have indicated that microRNAs (miRNAs) are involved in virus-host relationship, and this led us to investigate its essential roles in the in vitro hNECs model derived from multiple donors. By comparing the differential expression of miRNAs upon IAV infection among animal and cell line studies, candidates were selected with focus on the initial immune response...
January 25, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28115805/hsa-mir-499-rs3746444-t-c-polymorphism-is-associated-with-increased-risk-of-coronary-artery-disease-in-a-chinese-population
#6
Weiqiang Chen, Donghua Shao, Haiyong Gu, Jie Gong, Jian Zhang
BACKGROUND: Coronary artery disease (CAD) is a complex disease resulting from a combination of environmental and genetic factors. We hypothesized that polymorphisms hsa-mir-499 rs3746444 T/C, IRAK1 rs3027898 C/A and RANKL rs7984870 C/G might contribute to CAD susceptibility. METHODS: We studied the association between the three polymorphisms and the risk of CAD in a Chinese population using 435 CAD patients and 480 controls. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was used to perform the genotyping, and the differences were analysed...
January 2017: Acta Cardiologica Sinica
https://www.readbyqxmd.com/read/28099250/interleukin-36%C3%AE-induces-inflammatory-mediators-from-human-pancreatic-myofibroblasts-via-a-myd88-dependent-pathway
#7
Atsushi Nishida, Osamu Inatomi, Takehide Fujimoto, Hirotsugu Imaeda, Masaji Tani, Akira Andoh
OBJECTIVES: Interleukin 36 (IL-36) is a recently described proinflammatory cytokine, characterized by the induction of inflammatory mediators. In the present study, we investigated the biological activity and the signal transduction of IL-36α in human pancreatic myofibroblasts. METHODS: The mRNA and protein expression of inflammatory mediators was evaluated using real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. The expression of IL-36α and its receptor in the pancreatic tissue was evaluated using immunohistochemical technique...
January 18, 2017: Pancreas
https://www.readbyqxmd.com/read/28088700/chlorogenic-acid-ameliorated-concanavalin-a-induced-hepatitis-by-suppression-of-toll-like-receptor-4-signaling-in-mice
#8
Yinglin Yuan, Xia Gong, Li Zhang, Rong Jiang, Junxia Yang, Bin Wang, Jingyuan Wan
Chlorogenic acid (CGA), one of the most abundant dietary polyphenolic compounds, has been reported to exhibit anti-inflammatory ability. However, the hepatoprotective effects and molecular mechanisms of CGA on concanavalin A (Con A)-induced hepatitis have not been explored. In the present study, we found that pretreatment with CGA dose-dependently inhibited the elevation of plasma aminotransferases and alleviated hepatic pathological damage as well as hepatocyte apoptosis in Con A-exposed mice. Additionally, CGA markedly suppressed the production of serum tumor necrosis factor (TNF)-α and interferon (IFN)-γ, alleviated the infiltration of hepatic macrophages, neutrophils, and activated CD4(+) T lymphocytes in Con A-primed mice...
January 12, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28077577/extracellular-microrna-signature-of-human-helper-t-cell-subsets-in-health-and-autoimmunity
#9
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 T cell receptor stimulation, CD4(+) T helper (Th) 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 T cell receptor stimulation of Th1, Th17, and T regulatory (Treg) cells. Our results indicate that EVs released by Treg cells are significantly different compared with those released by the other subsets...
February 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28069966/inherited-human-irak-1-deficiency-selectively-impairs-tlr-signaling-in-fibroblasts
#10
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 24, 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
#11
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
#12
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
#13
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
#14
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
#15
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-facilitates-the-replication-of-porcine-reproductive-and-respiratory-syndrome-virus-by-its-negative-regulation-of-type-i-interferon-induction
#16
Jing Chen, Xibao Shi, Xiaozhuan Zhang, Aiping Wang, Li Wang, Yanyan Yang, Ruiguang Deng, Gai-Ping Zhang
: MicroRNAs (miRNAs) play an important role in the regulation of immune responses. Previous studies have indicated that dysregulating the miRNAs leads to the immunosuppression of porcine reproductive and respiratory syndrome virus (PRRSV). However, it is not clear how PRRSV regulates the expression of host miRNA, which may lead to immune escape or promote the replication of the virus. The present work suggests that PRRSV upregulated the expression of miR-373 through elevating the expression of specificity protein 1 (Sp1) in MARC-145 cells...
February 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/27864528/irak1-and-irak4-promote-phosphorylation-ubiquitination-and-degradation-of-myd88-adaptor-like-mal
#17
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
#18
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
#19
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
#20
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
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