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• W2040251623 abstract "HSP90에 노출된 혈관평활근세포에서 IL-6 transcript가 증가하고, IL-6 단백질의 분비가 증가하며, 또한 IL-6 유전자의 promote가 활성화되었다. HSP90에 의한 IL-6 유전자의 promoter 활성화는 dominant negative 형태의 TLR-4와 MyD88에 의하여 크게 감소되었지만, dominant negative 형태의 TLR-3와 TRIF의 영향을 받지 않았다. 그리고 TLR-4의 이합체화(dimerization)를 저해하는 curcumin은 HSP90에 의한 IL-6의 분비 및 IL-6 유전자 promoter 활성화를 억제하였다. 그리고 IL-6 유전자의 promoter의 NF-<TEX>${kappa}B$</TEX>- 또는 C/EBP-binding sequence에 변이는 HSP90에 의한 IL-6 유전자의 promoter 활성화 억제하였다. 이러한 결과는 혈관평활근세포에서 HSP90에 의한 IL-6 유전자 활성화에 TLR-4와 NF-<TEX>${kappa}B$</TEX>B가 관여함을 의미한다. This study has investigated whether extracellular HSP90 predisposes vascular smooth muscle cells (VSMCs) to pro-inflammatory phenotype. Exposure of rat aortic smooth muscle cells to HSP90 not only enhanced IL-6 release but also profoundly induced IL-6 transcript via promoter activation. HSP90-induced IL-6 promoter activation was suppressed by dominant-negative forms of Toll-like receptor (TLR)-4 and myeloid differentiation factor 88 (MyD88), but not by dominant-negative-forms of TLR-3 and TIR-domain-containing adapter-inducing interferon-<TEX>${beta}$</TEX> (TRIF). Curcumin, which inhibits dimerization of TLR-4, also attenuated the IL-6 induction by HSP90. Mutation at the NF-<TEX>${kappa}B$</TEX>- or C/EBP-binding site in the IL-6 promoter region suppressed the promoter activation in response to HSP90. The gene delivery of <TEX>$I{kappa}B$</TEX> using recombinant adenoviruses and treatment with resveratrol, which inhibit NF-<TEX>${kappa}B$</TEX> activity, attenuated the HSP90-induced IL-6 release from VSMCs. The present study proposes that extracellular HSP90 would contribute to inflammatory reaction in the stressed vasculature by inducing IL-6 in VSMCs, and that TLR-4 and NF-<TEX>${kappa}B$</TEX> would play active roles in the process." @default.
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• W2040251623 date "2008-12-30" @default.
• W2040251623 modified "2023-09-24" @default.
• W2040251623 title "Roles of TLR-4 and NF-κB in Interleukin-6 Expression Induced by Heat Shock Protein 90 in Vascular Smooth Muscle Cells" @default.
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• W2040251623 doi "https://doi.org/10.5352/jls.2008.18.12.1637" @default.
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