کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10815617 | 1058489 | 2011 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Activation of the PI3K pathway increases TLR-induced TNF-α and IL-6 but reduces IL-1β production in mast cells
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کلمات کلیدی
LPSFcεR1MD-2BMMCIL-33c-kitTLRIGF-1IL-1βPMCIL-6insulin - انسولینinsulin-like growth factor-1 - انسولین مانند عامل رشد 1Interleukin-33 - اینترلوکین 33interleukin-6 - اینترلوکین ۶Interleukin-1 beta - اینترلوکین-1 بتاtumor necrosis factor-α - تومور نکروز عامل αTIR - تیرToll-like receptor - تیالآرbone marrow-derived mast cell - سلول های مشتق شده از مغز استخوانPeritoneal mast cell - سلول های مغز پریتونالmyeloid differentiation factor 2 - عامل تمایز میلوئید 2TNF-α - فاکتور نکروز توموری آلفاlipopolysaccharide - لیپوپلی ساکاریدMast cell - ماستسلPropidium iodide - پروتئین یدید
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
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چکیده انگلیسی
Recognition of bacterial constituents by mast cells (MCs) is dependent on the presence of pattern recognition receptors, such as Toll-like receptors (TLRs). The final cellular response, however, depends on the influence of multiple environmental factors. In the current study we tested the hypothesis that the PI3K-activating ligands insulin-like growth factor-1 (IGF-1), insulin, antigen, and Steel Factor (SF) are able to modulate the TLR4-mediated production of proinflammatory cytokines in murine MCs. Costimulation with any of these ligands caused increased LPS-triggered secretion of IL-6 and TNF-α, but attenuated the production of IL-1β, though all three cytokines were produced in an NFκB-dependent manner. The pan-specific PI3K-inhibitor Wortmannin reverted the altered production of these cytokines. In agreement, MCs deficient for SHIP1, a negative regulator of the PI3K pathway, showed augmented secretion of IL-6/TNF-α and reduced production of IL-1β in response to LPS alone. The differential effects of IGF-1 on TLR4-mediated cytokine production were also observed in the context of TLR2 and IL-33 receptor-mediated MC activation. Importantly, these effects were seen in both bone marrow-derived and peritoneal MCs, suggesting general relevance for MCs. Using pharmacological and genetic tools, we could show that the p110δ isoform of PI3K is strongly implicated in SF-triggered suppression of LPS-induced IL-1β production. Costimulation with antigen was affected to a lesser extent. In conclusion, NFκB-dependent production of proinflammatory cytokines in MCs is differentially controlled by PI3K-activating ligand/receptor systems.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cellular Signalling - Volume 23, Issue 5, May 2011, Pages 866-875
Journal: Cellular Signalling - Volume 23, Issue 5, May 2011, Pages 866-875
نویسندگان
Thomas Hochdörfer, Marcel Kuhny, Carolin N. Zorn, Rudi W. Hendriks, Bart Vanhaesebroeck, Thomas Bohnacker, Gerald Krystal, Michael Huber,