کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2832021 1570739 2010 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Mammalian target of rapamycin (mTOR) regulates TLR3 induced cytokines in human oral keratinocytes
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شناسی مولکولی
پیش نمایش صفحه اول مقاله
Mammalian target of rapamycin (mTOR) regulates TLR3 induced cytokines in human oral keratinocytes
چکیده انگلیسی

Recent studies implicate the mammalian target of rapamycin (mTOR) pathway in the control of inflammatory responses following Toll-like receptor (TLR) stimulation in myeloid cells but its role in non-myeloid cells such as human keratinocytes is unknown. Here we show that TLR3 signaling can induce robust cytokine secretion including interleukin 1 beta (IL-1β), tumor necrosis factor alpha (TNFα), IL-12p70 and interferon beta (IFN-β), and our data reveal for the first time that inhibiting mTOR with rapamycin, suppresses these TLR3 induced responses but actually enhances bioactive IL-12p70 production in human oral keratinocytes. Rapamycin inhibited the phosphorylation of the 70-kDa ribosomal protein S6 kinase (p70S6K) and the 4E binding protein 1 (4EBP-1), and suppressed the mitogen activated protein kinase (MAPK) pathway by decreasing phosphorylation of c-Jun N-terminal kinase (JNK). We also show that TLR3 induces interferon regulatory factor 3 (IRF3) activation by Akt via an mTOR–p70S6K–4EBP1 pathway. Furthermore, we provide evidence that Poly I:C induced expression of IL-1β, TNFα, IL-12p70 and IFN-β was blocked by JNK inhibitor SP600125. TLR3 preferentially phosphorylated IKKα through mTOR to activate nuclear factor kappa beta (NF-κB) in human oral keratinocytes. Taken together, these data demonstrate p70S6K, p4EBP1, JNK, NF-κB and IRF3 are involved in the regulation of inflammatory mediators by TLR3 via the mTOR pathway. mTOR is a novel pathway modulating TLR3 induced inflammatory and antiviral responses in human oral keratinocytes.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular Immunology - Volume 48, Issues 1–3, November–December 2010, Pages 294–304
نویسندگان
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