Toll-like receptor 3 upregulation by type I interferon in healthy and scleroderma dermal fibroblasts.
Toll-like receptor 3 upregulation by type I interferon in healthy and scleroderma dermal fibroblasts.
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DOI：
10.1186/ar3221
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发表时间：
2011-01-11
影响因子：
4.9
通讯作者：
Tan FK
中科院分区：
文献类型：
--
作者：
Agarwal SK;Wu M;Livingston CK;Parks DH;Mayes MD;Arnett FC;Tan FK
在系统性硬化症（SSc）或硬皮病患者中观察到I型干扰素（IFN）途径中基因水平升高。I型IFN如何调节真皮成纤维细胞及其参与真皮纤维化的发展尚不清楚。我们假设I型IFN可能导致真皮纤维化的一种机制是通过上调真皮成纤维细胞上的特异性Toll样受体（TLR）。因此，我们研究了IFN对真皮成纤维细胞TLR表达的调节。在来自对照和用IFNα2刺激的SSc患者的培养的真皮成纤维细胞中评估TLR的表达。还评估了IFNα2调节TLR诱导的白细胞介素（IL）-6和CC趋化因子配体2产生的能力。进行免疫组织化学分析，以确定TLR 3是否在博莱霉素诱导的皮肤纤维化模型和SSc患者的皮肤活检组织中表达。IFNα2增加人皮肤成纤维细胞上TLR 3的表达，这导致TLR 3诱导的IL-6产生增加。相对于对照成纤维细胞，SSc成纤维细胞对IFNα2的TLR 3应答增强。用转化生长因子（TGF）-β预处理成纤维细胞可增加IFNα2对TLR 3的诱导，但TGF-β共孵育不能改变IFNα2对TLR 3的诱导。此外，IFNα2抑制但不完全阻断成纤维细胞中TGF-β诱导结缔组织生长因子和胶原表达。在SSc患者皮肤活检组织的真皮成纤维细胞和炎性细胞中以及博来霉素诱导的皮肤纤维化模型中观察到TLR 3表达。I型IFN可通过上调TLR 3增加真皮成纤维细胞的炎症潜能。
Increased levels of genes in the type I interferon (IFN) pathway have been observed in patients with systemic sclerosis (SSc), or scleroderma. How type I IFN regulates the dermal fibroblast and its participation in the development of dermal fibrosis is not known. We hypothesized that one mechanism by which type I IFN may contribute to dermal fibrosis is through upregulation of specific Toll-like receptors (TLRs) on dermal fibroblasts. Therefore, we investigated the regulation of TLR expression on dermal fibroblasts by IFN. The expression of TLRs was assessed in cultured dermal fibroblasts from control and SSc patients stimulated with IFNα2. The ability of IFNα2 to regulate TLR-induced interleukin (IL)-6 and CC chemokine ligand 2 production was also assessed. Immunohistochemical analyses were performed to determine whether TLR3 was expressed in skin biopsies in the bleomycin-induced skin fibrosis model and in patients with SSc. IFNα2 increased TLR3 expression on human dermal fibroblasts, which resulted in enhanced TLR3-induced IL-6 production. SSc fibroblasts have an augmented TLR3 response to IFNα2 relative to control fibroblasts. Pretreatment of fibroblasts with transforming growth factor (TGF)-β increased TLR3 induction by IFNα2, but coincubation of TGF-β did not alter TLR3 induction by IFN. Furthermore, IFNα2 inhibits but does not completely block the induction of connective tissue growth factor and collagen expression by TGF-βin fibroblasts. TLR3 expression was observed in dermal fibroblasts and inflammatory cells from skin biopsies from patients with SSc as well as in the bleomycin-induced skin fibrosis model. Type I IFNs can increase the inflammatory potential of dermal fibroblasts through the upregulation of TLR3.
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影响因子：
6
作者：
Lakos, G;Takagawa, S;Varga, J
通讯作者：
Varga, J
DOI：
10.1073/pnas.0700021104
发表时间：
2007-02-20
影响因子：
11.1
作者：
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通讯作者：
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影响因子：
27.4
作者：
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通讯作者：
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影响因子：
56.9
作者：
Blanco, P;Palucka, AK;Banchereau, J
通讯作者：
Banchereau, J
影响因子：
15.9
作者：
DUNCAN, MR;BERMAN, B
通讯作者：
BERMAN, B