Requirement of TLR2-mediated signaling for the induction of IL-15 gene expression in human monocytic cells by HSV-1
| العنوان: | Requirement of TLR2-mediated signaling for the induction of IL-15 gene expression in human monocytic cells by HSV-1 |
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| المؤلفون: | Paulo Cordeiro, Souad El Bassam, José Menezes, Rasheed Ahmad |
| المصدر: | Blood. 112:2360-2368 |
| بيانات النشر: | American Society of Hematology, 2008. |
| سنة النشر: | 2008 |
| مصطلحات موضوعية: | TIRAP, Small interfering RNA, Immunology, Herpesvirus 1, Human, Biology, Biochemistry, Monocytes, Gene expression, Humans, RNA, Small Interfering, Interleukin-15, TNF Receptor-Associated Factor 6, Membrane Glycoproteins, NF-kappa B, Receptors, Interleukin-1, Signal transducing adaptor protein, IRAK1, Cell Biology, Hematology, Molecular biology, Toll-Like Receptor 2, Protein Transport, TLR2, Interleukin-1 Receptor-Associated Kinases, Gene Expression Regulation, Interleukin 15, Myeloid Differentiation Factor 88, Signal transduction, Signal Transduction |
| الوصف: | Exposure of human monocytic cells to herpes simplex virus type 1 (HSV-1) results in immediate up-regulation of interleukin (IL)–15 gene expression. However, the receptor involved in this induction is not known. Here, we provide evidence that this induction depends on TLR2-mediated signaling pathway. Through the use of small interfering RNAs (siRNAs), we demonstrate that HSV-1–induced up-regulation of IL-15 gene expression in monocytic THP1 cells requires the presence of the adaptors MyD88, IRAK1, and TRAF6. Interestingly, TIRAP/Mal, an adaptor molecule specifically recruited to TLR2 and TLR4, was also required for maximal up-regulation of IL-15. This response was completely abrogated by anti-TLR2, but not anti-TLR4, blocking mAbs in both primary monocytes and THP1 cells. Furthermore, THP1 cells rendered defective in TLR2 expression by disrupting the expression of Sp1, a major transcription factor involved in TLR2 promoter activity, were unable to up-regulate IL-15 gene expression in response to HSV-1. In addition, HSV-1–induced NF-κB activation was significantly reduced after neutralization of TLR2 and the adaptor proteins. Altogether, these results unequivocally show that HSV-1 induces TLR2-dependent activation of IL-15 gene expression, which requires the recruitment of both MyD88 and TIRAP/Mal and the activation of IRAK1 and TRAF6 leading to NF-κB translocation to the nucleus. |
| تدمد: | 1528-0020 0006-4971 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::017c07f93e137e7bfec26538784c0f80Test https://doi.org/10.1182/blood-2008-02-137711Test |
| رقم الانضمام: | edsair.doi.dedup.....017c07f93e137e7bfec26538784c0f80 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15280020 00064971 |
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