Interleukin-4 and interleukin-13 enhance CCL26 production in a human keratinocyte cell line, HaCaT cells
Interleukin-4 and interleukin-13 enhance CCL26 production in a human keratinocyte cell line, HaCaT cells
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DOI：
10.1111/j.1365-2249.2005.02875.x
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发表时间：
2005-09-01
影响因子：
4.6
通讯作者：
Tamaki, K
中科院分区：
文献类型：
--
作者：
Kagami, S;Saeki, H;Tamaki, K
Eotaxin-2/CCL 24和Eotaxin-3/CCL 26是CC趋化因子及其受体，CC趋化因子受体3优先在嗜酸性粒细胞上表达。据报道，血管内皮细胞和真皮成纤维细胞产生CCL 26。然而，角质形成细胞中CCL 24和CCL 26产生的调节尚未得到充分记载。我们研究了CCL 24和CCL 26在人角质形成细胞系HaCaT细胞中的表达和产生。使用这些细胞进行逆转录和聚合酶链反应，并使用这些细胞的上清液进行酶联免疫吸附测定。HaCaT细胞中CCL 24的产生被IL-4轻微增强，而CCL 26的产生被IL-4和IL-13强烈增强。此外，TNF-α对IL-4增强的CCL 26产生产生协同作用。地塞米松、IFN-γ和p38丝裂原活化蛋白激酶抑制剂SB 202190抑制IL-4增强的CCL 26产生。来氟米特和JAK抑制剂1可抑制IL-4促进CCL 26的产生，而JAK 3抑制剂则不抑制IL-4促进CCL 26的产生，提示IL-4促进CCL 26的产生是通过JAK 1-STAT 6依赖性途径介导的。该结果也强烈地表明2型IL-4受体参与IL-4增强的CCL 26的产生。这些结果表明，角质形成细胞参与CC趋化因子受体3阳性细胞的迁移，如嗜酸性粒细胞在Th 2-显性的情况下，如特应性皮炎。
Eotaxin-2/CCL24 and eotaxin-3/CCL26 are CC chemokines and their receptor, CC chemokine receptor 3 is preferentially expressed on eosinophils. It was reported that vascular endothelial cells and dermal fibroblasts produced CCL26. However, the regulation of CCL24 and CCL26 production in keratinocytes has not been well documented. We investigated the expression and production of CCL24 and CCL26 in the human keratinocyte cell line, HaCaT cells. Reverse transcription and polymerase chain reaction was performed using these cells and Enzyme-linked immunosorbent assay was carried out using supernatant of these cells. The production of CCL24 in HaCaT cells was slightly enhanced by IL-4 and that of CCL26 was strongly enhanced by IL-4 and IL-13. Furthermore, TNF-alpha generated a synergistic effect on IL-4 enhanced CCL26 production. Dexamethasone, IFN-gamma and the p38 mitogen-activated protein kinase inhibitor SB202190 inhibited IL-4 enhanced CCL26 production. IL-4 enhanced production of CCL26 was inhibited by leflunomide and JAK inhibitor 1, but not by JAK3 inhibitor, which indicates that it is mediated by JAK1-STAT6-dependent pathway. This result also strongly suggests the involvement of the type 2 IL-4 receptor in IL-4 enhanced production of CCL26. These results suggest that keratinocytes are involved in the migration of CC chemokine receptor 3 positive cells such as eosinophils in a Th2-dominant situation like atopic dermatitis.