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https://www.readbyqxmd.com/read/28739486/microrna-146a-5p-attenuates-liver-fibrosis-by-suppressing-profibrogenic-effects-of-tgf%C3%AE-1-and-lipopolysaccharide
#1
Yanting Zou, Yu Cai, Di Lu, Yi Zhou, Qunyan Yao, Shuncai Zhang
Liver fibrosis is characterized by proliferation and activation of hepatic stellate cells (HSCs). Transforming growth factor-β1 (TGFβ1) is crucial for liver fibrogenesis, and gut-derived endotoxin (LPS) also plays an important role in liver fibrogenesis. In the present study, we found that microRNA-146a-5p (miR-146a-5p) could regulate TGFβ1/Smad and LPS/NF-κB/Bambi pathways to attenuate liver fibrosis. Downregulated miR-146a-5p and upregulated level of LPS were found in liver of CCl4-treated rats. On cellular level, expression of miR-146a-5p is reduced during primary rat HSCs naturally activation and changed in response to TGFβ1 and/or LPS stimulation in primary rat HSCs and human HSC line LX-2...
July 21, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28731142/nlrc3-promotes-host-resistance-against-pseudomonas-aeruginosa-induced-keratitis-by-promoting-the-degradation-of-irak1
#2
Litao Guo, Qingzhu Kong, Zhijun Dong, Weili Dong, Xiaoxiao Fu, Leqi Su, Xiaobo Tan
Pseudomonas aeruginosa (PA)-induced keratitis is one of the most common and destructive bacterial diseases. The pathogenesis of PA infections is closely associated with excessive inflammatory responses. Nucleotide oligomerization domain (NOD)-like receptor (NLR) family with caspase activation and recruitment domain (CARD) containing 3 (NLRC3) protein has been implicated as a negative regulator of inflammation and antiviral response, but the role of NLRC3 in PA-induced keratitis has not been described...
July 20, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28714001/lps-enhances-tlr4-expression-and-ifn%C3%A2-%C3%AE-production-via-the-tlr4-irak-nf%C3%A2-%C3%AE%C2%BAb-signaling-pathway-in-rat-pulmonary-arterial-smooth-muscle-cells
#3
Pengyan Wang, Xuhui Han, Biwen Mo, Guojin Huang, Changming Wang
The aim of the present study was to investigate the role of the Toll‑like receptor (TLR)4 signaling pathway in cellular response to lipopolysaccharide (LPS) in rat pulmonary artery smooth muscle cells (PASMCs). Chronic obstructive pulmonary disease (COPD) rats were established with passive inhaling cigarette smoke plus injection of LPS. The TLR4 protein in lung tissues was determined with immunohistochemical staining and protein levels of the components of the TLR4 pathway in PASMCs were analyzed with western blotting...
September 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28684329/house-dust-mite-increases-pro-th2-cytokines-il-25-and-il-33-via-the-activation-of-tlr1-6-signaling
#4
Yong Hyun Jang, Jin Kyeong Choi, Meiling Jin, Young-Ae Choi, Zae Young Ryoo, Hyun-Shik Lee, Pil-Hoon Park, Sun-Uk Kim, Taeg Kyu Kwon, Myoung Ho Jang, Sin-Hyeog Im, Sun Young Moon, Weon Ju Lee, Seok-Jong Lee, Do Won Kim, Sang-Hyun Kim
House dust mite (HDM) has been implicated in the etiology and exacerbation of atopic dermatitis (AD). Diverse factors contribute to HDM allergenicity through the activation of innate immunity. We investigated whether Dermatophagoides farinae extract (DFE) allergens mediate innate immune activation through specific Toll-like receptors (TLRs) in epidermal keratinocytes, DFE-induced murine AD model and human AD lesions. DFE activated the expression of TLR1, TLR6, interleukin (IL)-25, and IL-33 in human primary keratinocytes and HaCaT cells...
July 3, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28680194/syk-plays-a-critical-role-in-the-expression-and-activation-of-irak1-in-lps-treated-macrophages
#5
Jae Gwang Park, Young-Jin Son, Byong Chul Yoo, Woo Seok Yang, Ji Hye Kim, Jong-Hoon Kim, Jae Youl Cho
To address how interleukin-1 receptor-associated kinase 1 (IRAK1) is controlled by other enzymes activated by toll-like receptor (TLR) 4, we investigated the possibility that spleen tyrosine kinase (Syk), a protein tyrosine kinase that is activated at an earlier stage during TLR4 activation, plays a central role in regulating the functional activation of IRAK1. Indeed, we found that overexpression of myeloid differentiation primary response gene 88 (MyD88), an adaptor molecule that drives TLR signaling, induced IRAK1 expression and that piceatannol, a Syk inhibitor, successfully suppressed the MyD88-dependent upregulation of IRAK1 under LPS treatment conditions...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28668488/glycyrrhetinic-acid-prevents-acetaminophen-induced-acute-liver-injury-via-the-inhibition-of-cyp2e1-expression-and-hmgb1-tlr4-signal-activation-in-mice
#6
Genling Yang, Li Zhang, Li Ma, Rong Jiang, Ge Kuang, Ke Li, Hongtao Tie, Bin Wang, Xinyu Chen, Tianjun Xie, Xia Gong, Jingyuan Wan
Acetaminophen (APAP) is a widely used antipyretic and analgesic drug, which is safe and effective at the therapeutic dose. Unfortunately, excessive dosage of APAP could cause severe liver injury due to lack of effective therapy. Successful therapeutic strategies are urgently requested in clinic. Glycyrrhetinic acid (GA), derived from a traditional medicine licorice, has been shown to exert anti-inflammatory and antioxidant actions. In this study, the effect and the underlying mechanism of GA on APAP-induced hepatotoxicity were explored...
June 29, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28659487/mumps-virus-sh-protein-inhibits-nf-%C3%AE%C2%BAb-activation-by-interacting-with-tnfr1-il-1r1-and-tlr3-complexes
#7
Stephanie Franz, Paul Rennert, Maria Woznik, Josephine Grützke, Amy Lüdde, Eva Maria Arriero Pais, Tim Finsterbusch, Henriette Geyer, Annette Mankertz, Nicole Friedrich
The mumps virus (MuV) small hydrophobic protein (SH) is a type I membrane protein expressed in infected cells. SH has been reported to interfere with innate immunity by inhibiting TNFα-mediated apoptosis and NF-κB activation. To elucidate the underlying mechanism, we generated recombinant MuVs (rMuVs) expressing either the SH protein with an N-terminal FLAG epitope or lacking SH expression due to the insertion of three stop codons into the SH gene. Using these viruses, we were able to show that SH reduces the phosphorylation of IKKβ, IκBα, and p65 as well as the translocation of p65 into the nucleus of infected A549 cells...
June 28, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28659029/the-mixture-of-anemarrhena-asphodeloides-and-coptis-chinensis-attenuates-high-fat-diet-induced-colitis-in-mice
#8
Su-Min Lim, Hyun-Sik Choi, Dong-Hyun Kim
Anemarrhena asphodeloides (AA, family Liliaceae) inhibits macrophage activation by inhibiting IRAK1 phosphorylation and helper T (Th)17 differentiation. Coptis chinensis (CC, family Ranunculaceae), which inhibits macrophage activation by inhibiting the binding of lipopolysaccharide (LPS) on toll-like receptor 4 and inducing regulatory T (Treg) cell differentiation. The mixture of AA and CC (AC-mix) synergistically attenuates 2,4,6-trinitrobenzenesulfonic acid or dextran sulfate sodium-induced colitis in mice by inhibiting NF-[Formula: see text]B activation and regulating Th17/Treg balance...
June 28, 2017: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/28587864/up-regulation-of-circulating-mirna146a-correlates-with-viral-load-via-irak1-and-traf6-in-hepatitis-c-virus-infected-patients
#9
Fayda Ibrahim Abdel Motaleb, Enas Samir Nabih, Sherif Moneir Mohamed, Nehal Samir Abd Elhalim
BACKGROUND: Hepatitis C virus (HCV) is a life threatening human pathogen. It has been found that miRNA146a regulates innate immunity, inflammatory response and antiviral pathway. We evaluated miRNA146a expression by real-time PCR and IL-1 receptor associated kinase 1 (IRAK1) and TNF receptor-associated factor 6 (TRAF6) levels by ELISA in serum of 36 HCV viremia patients and 42 age and gender matched healthy controls. RESULTS: miRNA146a expression was significantly higher in HCV patients with a best cut off value 1...
June 3, 2017: Virus Research
https://www.readbyqxmd.com/read/28572512/deletion-of-interleukin-1-receptor-associated-kinase-1-irak1-improves-glucose-tolerance-primarily-by-increasing-insulin-sensitivity-in-skeletal-muscle
#10
Xiao Jian Sun, Soohyun Park Kim, Dongming Zhang, Helen Sun, Qi Cao, Xin Lu, Zhekang Ying, Liwu Li, Robert R Henry, Theodore P Ciaraldi, Simeon I Taylor, Michael J Quon
Chronic inflammation may contribute to insulin resistance (IR) via molecular cross-talk between pathways for pro-inflammatory and insulin signaling. Interleukin 1 receptor associated kinase 1 (IRAK1) mediates pro-inflammatory signaling via IL-1 receptor/Toll-like receptors, which may contribute to insulin resistance, but this hypothesis is untested. Here, we used male Irak1 null (k/o) mice to investigate the metabolic role of IRAK1. C57BL/6 wild-type (WT) and k/o mice had comparable body weights on low-fat and high-fat diets (LFD and HFD, respectively)...
June 1, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28553204/leucine-rich-repeat-kinase-2-lrrk2-stimulates-il-1%C3%AE-mediated-inflammatory-signaling-through-phosphorylation-of-rcan1
#11
Kyung A Han, Lang Yoo, Jee Y Sung, Sun A Chung, Ji W Um, Hyeyoung Kim, Wongi Seol, Kwang C Chung
Leucine-rich repeat kinase 2 (LRRK2) is a Ser/Thr kinase having mixed lineage kinase-like and GTPase domains, controlling neurite outgrowth and neuronal cell death. Evidence suggests that LRRK2 is involved in innate immune response signaling, but the underlying mechanism is yet unknown. A novel protein inhibitor of phosphatase 3B, RCAN1, is known to positively regulate inflammatory signaling through modulation of several intracellular targets of interleukins in immune cells. In the present study, we report that LRRK2 phosphorylates RCAN1 (RCAN1-1S) and is markedly up-regulated during interleukin-1β (IL-1β) treatment...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28536249/bronchial-inflammation-and-bacterial-load-in-stable-copd-is-associated-with-tlr4-overexpression
#12
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
#13
COMPARATIVE STUDY
Stefan Vollmer, Sam Strickson, Tinghu Zhang, Nathanael Gray, Katherine L Lee, Vikram R 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...
June 6, 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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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 [160mg/kg], middle dose [80mg/kg] and low dose [40mg/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 respectively...
July 12, 2017: Journal of Ethnopharmacology
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