Regulatory mechanisms of galectin-9 and eotaxin-3 synthesis in epidermal keratinocytes: possible involvement of galectin-9 in dermal eosinophilia of Th1-polarized skin inflammation
Regulatory mechanisms of galectin-9 and eotaxin-3 synthesis in epidermal keratinocytes: possible involvement of galectin-9 in dermal eosinophilia of Th1-polarized skin inflammation
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DOI：
10.1111/j.1398-9995.2006.01130.x
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发表时间：
2006-12-01
期刊：
影响因子：
12.4
通讯作者：
Yokozeki, H.
中科院分区：
文献类型：
--
作者：
Igawa, K.;Satoh, T.;Yokozeki, H.
背景资料：皮肤嗜酸性粒细胞增多是过敏性皮肤病的常见特征，但目前尚不清楚如何控制表皮和真皮嗜酸性粒细胞浸润。为了研究嗜酸性粒细胞在皮肤中的定位调节，我们研究了真皮成纤维细胞和表皮角质形成细胞中嗜酸性粒细胞特异性趋化因子表达的调节机制。方法：我们分析了真皮成纤维细胞和表皮角质形成细胞在体外对几种刺激的反应中产生的嗜酸性粒细胞趋化因子，嗜酸性粒细胞趋化因子-2，嗜酸性粒细胞趋化因子-3和半乳糖凝集素-9。真皮成纤维细胞产生嗜酸性粒细胞趋化因子和嗜酸性粒细胞趋化因子-3响应于白细胞介素（IL）-4和/或肿瘤坏死因子-α的刺激。类似地，IL-4刺激表皮角质形成细胞分泌嗜酸性粒细胞趋化因子-3。然而，我们没有检测到eotaxin的mRNA表达或蛋白分泌的角质形成细胞在体外刺激。干扰素（IFN）-γ诱导真皮成纤维细胞上的半乳糖凝集素-9表达。相反，半乳糖凝集素-9在表皮角质形成细胞上的表达被IFN-γ剂量依赖性地抑制。免疫组化结果显示，寻常型银屑病皮损中的真皮成纤维细胞（而非表皮角质形成细胞）表达高水平的galectin-9。结论：Eotaxin-3参与了产生IL-4的Th 2极化皮肤炎症中真皮和表皮嗜酸性粒细胞的浸润。相比之下，IFN-γ主导的炎症似乎介导嗜酸性粒细胞外渗到真皮中，并介导嗜酸性粒细胞通过半乳糖凝集素-9粘附到真皮成纤维细胞，这与表皮半乳糖凝集素-9的化学引诱物活性降低有关。本研究结果揭示了一种新的机制，真皮嗜酸性粒细胞在IFN-γ介导的皮肤炎症，并反映协调化学引诱物的生产涉及真皮和/或表皮嗜酸性粒细胞在局部细胞因子谱的变化。
Background: Skin eosinophilia is a common feature of allergic skin diseases, but it is unclear how epidermal and dermal eosinophil infiltration is controlled. To investigate regulation of localization of eosinophils in skin, we examined the regulatory mechanisms of expression of eosinophil-specific chemoattractants in dermal fibroblasts and epidermal keratinocytes.Methods: We analyzed production of eotaxin, eotaxin-2, eotaxin-3 and galectin-9 by dermal fibroblasts and epidermal keratinocytes in response to several stimuli in vitro.Results: Dermal fibroblasts produced eotaxin and eotaxin-3 in response to stimulation by interleukin (IL)-4 and/or tumor necrosis factor-alpha. Similarly, IL-4 stimulated epidermal keratinocytes to secrete eotaxin-3. However, we did not detect eotaxin mRNA expression or protein secretion by keratinocytes stimulated in vitro. Interferon (IFN)-gamma induced galectin-9 expression on dermal fibroblasts. Conversely, expression of galectin-9 on epidermal keratinocytes was dose-dependently inhibited by IFN-gamma. The immunohistochemical assays revealed that dermal fibroblasts (but not epidermal keratinocytes) in the lesional skin of psoriasis vulgaris (a Th1-polarized disease) express significant levels of galectin-9.Conclusions: Eotaxin-3 contributes to dermal and epidermal eosinophil infiltration in Th2-polarized skin inflammation in which IL-4 is produced. In contrast, IFN-gamma-dominated inflammation appears to mediate eosinophil extravasation into the dermis and eosinophil adhesion to dermal fibroblasts via galectin-9 in association with decreased chemoattractant activity of epidermal galectin-9. The present results reveal a novel mechanism of dermal eosinophilia in IFN-gamma-mediated skin inflammation, and reflect concerted chemoattractant production involving dermal and/or epidermal eosinophilia during changes in the local cytokine profile.