کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10815464 | 1058475 | 2013 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Combined CpG and poly I:C stimulation of monocytes results in unique signaling activation not observed with the individual ligands
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کلمات کلیدی
MK2Rac1AP-1DCsPKCPBMCsPKBASK1PRRsTBK1TAK1JAK-STATJun N-terminal kinasePLCγBLNKSTRINGMKK3Mitogen-activated protein kinase-activated protein kinase 2MKK6Phospholipase C gammaribosomal S6 kinase 1CaMK2mitogen-activated protein kinase kinase 3B cell Linker proteinKEGGCREBPI3KJnkCpGRAFPAMPsERKRASiNOSBtk - BTKC/EBP - C / EBPMAPK - MAPKNFκB - NFKBTLRs - TLR هاPeptide array - آرایه پپتیدهAkt - آکتSearch Tool for the Retrieval of Interacting Genes - ابزار جستجو برای بازیابی ژن های تعاملpathogen-associated molecular patterns - الگوهای مولکولی مرتبط با پاتوژنBruton tyrosine kinase - بروتون تیروزین کینازTANK-binding kinase 1 - تین کیناز 1Kyoto Encyclopedia of Genes and Genomes - دایره المعارف ژنتیک ژن ها و ژنوم کیوتوRas-related C3 botulinum toxin substrate 1 - زیر بغل سم بوتولینوم C3 مرتبط با ریز 1CAM - ساخت به کمک کامپیوترrat sarcoma - سارکوم موش صحراییperipheral blood mononuclear cells - سلول های تک هسته ای خون محیطیDendritic cells - سلول های دندریتیکinducible nitric oxide synthase - سنتاز اکسید نیتریک القاییSignaling - سیگنالینگnuclear factor κB - فاکتور هسته ای κBphosphoinositide 3-kinase - فسفینوزیتید 3-کینازrapidly accelerated fibrosarcoma - فیبروسارکوم سریعا شتاب می گیردNitric oxide - نیتریک اکسیدCCAAT/enhancer binding protein - پروتئین اتصال CCAAT / enhanceractivator protein 1 - پروتئین فعال کننده 1cAMP response element-binding protein - پروتئین واکنش القا کننده واکنش cAMPprotein kinase B - پروتئین کیناز BProtein kinase C - پروتئین کیناز سیmitogen-activated protein kinase - پروتئین کیناز فعال با mitogenPoly I:C - پلی I: CPolyinosinic–polycytidylic acid - پلیسی سمی-پلیسییدیدیل اسیدCalmodulin - کالمودولینKinase - کینازapoptosis signal-regulating kinase 1 - کیناز تنظیم کننده سیگنال آپوپتوز 1extracellular signal-regulated kinases - کیناز های تنظیم شده سیگنال خارج سلولیpattern recognition receptors - گیرنده های تشخیص الگوToll-like receptors - گیرنده های پولی مانند
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Toll-like receptors (TLRs) bind to components of microbes, activate cellular signal transduction pathways and stimulate innate immune responses. Previously, we have shown in chicken monocytes that the combination of CpG, the ligand for TLR21 (the chicken equivalent of TLR9), and poly I:C, the ligand for TLR3, results in a synergistic immune response. In order to further characterize this synergy, kinome analysis was performed on chicken monocytes stimulated with either unmethylated CpG oligodeoxynucleotides (CpG) and polyinosinic-polycytidylic acid (poly I:C) individually or in combination for either 1 h or 4 h. The analysis was carried out using chicken species-specific peptide arrays to study the kinase activity induced by the two ligands. The arrays are comprised of kinase target sequences immobilized on an array surface. Active kinases phosphorylate their respective target sequences, and these phosphorylated peptides are then visualized and quantified. A significant number of peptides exhibited altered phosphorylation when CpG and poly I:C were given together, that was not observed when either CpG or poly I:C was given separately. The unique, synergistic TLR agonist affected peptides represent protein members of signaling pathways including calcium signaling pathway, cytokine-cytokine receptor interaction and Endocytosis at the 1 h time point. At the 4 h time point, TLR agonist synergy influenced pathways included Adipocytokine signaling pathway, cell cycle, calcium signaling pathway, NOD-like receptor signaling pathway and RIG-I-like receptor signaling pathway. Using nitric oxide (NO) production as the readout, TLR ligand synergy was also investigated using signaling protein inhibitors. A number of inhibitors were able to inhibit NO response in cells given CpG alone but not in cells given both CpG and poly I:C, as poly I:C alone does not elicit a significant NO response. The unique peptide phosphorylation induced by the combination of CpG and poly I:C and the unique signaling protein requirements for synergy determined by inhibitor assays both show that synergistic signaling is not a simple addition of TLR pathways. A set of secondary pathways activated by the ligand combination are proposed, leading to the activation of cAMP response element-binding protein (CREB), nuclear factor κB (NFκB) and ultimately of inducible nitric oxide synthase (iNOS). Since many microbes can stimulate more than one TLR, this synergistic influence on cellular signaling may be an important consideration for the study of immune response and what we consider to be the canonical TLR signaling pathways.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cellular Signalling - Volume 25, Issue 11, November 2013, Pages 2246-2254
Journal: Cellular Signalling - Volume 25, Issue 11, November 2013, Pages 2246-2254
نویسندگان
Ryan J. Arsenault, Michael H. Kogut, Haiqi He,