Productive role of fractalkine and CXCL16 in human epidermal keratinocytes

CXCL 16是CXCR 6的配体，CXCR 6是CXC趋化因子受体。CXCL 16以膜结合形式合成，其裂解为可溶性形式，该可溶性形式是表达CXCR 6的细胞如活化的CD 8 T细胞、NKT细胞和Th 1极化的CD 4和CD 8 T细胞的化学引诱物。相比之下，在人巨噬细胞和树突状细胞上表达的膜结合形式的CXCL 16充当氧化低密度脂蛋白的清道夫受体。此外，在巨噬细胞上表达的CXCL 16介导细菌如大肠杆菌或金黄色葡萄球菌的粘附和吞噬。浓度> 5 μ g/ml的CXCL 16的可溶性趋化因子结构域具有抗金黄色葡萄球菌和大肠杆菌的抗微生物活性。添加10 μ g/ml可溶性CXCL 16使金黄色葡萄球菌和大肠杆菌的存活率分别降低70%和40%。由于CXCL 16是由HEK组成性产生的，CXCL 16有助于与人类皮肤中的微生物病原体以及□-防御素相关的宿主防御功能。由于fractalkine募集CX 3CR 1阳性细胞，如NK细胞和CD 8 + T细胞，因此它应该参与将这些细胞募集到炎症反应中的表皮中。为了解决这个问题，我们研究了正常人角质形成细胞是否可以在细胞因子的存在下产生fractalkine。TNF-□、IL-1-□□和IFN-□协同增强正常人角质形成细胞中IFN-□诱导的Fractalkine产生。总之，这是第一份报告表明，正常人角质形成细胞产生可溶性fractalkine蛋白。

CXCL16 is a ligand for CXCR6, a CXC-chemokine receptor. CXCL16 is synthesized as a membrane-bound form that is cleaved to a soluble form that is a chemoattractant for CXCR6-expressing cells such as activated CD8 T cells, NKT cells, and Th1-polarized CD4 and CD8 T cells. By contrast, a membrane-bound form of CXCL16 expressed on human macrophages and dendritic cells acts as a scavenger receptor for oxidized low density lipoprotein. In addition, CXCL16 expressed on macrophages mediates adhesion and phagocytosis of bacteria such as Escheria coli or Staphylococcus aureus. The soluble chemokine domain of CXCL16 at concentrations > 5 □g/ml had antimicrobial activity against S.aureus and E.coli. Addition of 10 □g/ml soluble CXCL16 reduced the survival rate of S.aureus and E.coli by 70 and 40%, respectively. Because CXCL16 is produced constitutively by HEK, CXCL16 contributes to host-defense function in relation to microbial pathogens in human skin as well as □-defensins.Fractalkine/CX3CL1, a chemokine, is synthesized as a membrane bound form and converted to a soluble form by protease(s). Since fractalkine recruits CX3CR1 positive cells such as NK cells and CD8+ T cells, it is supposed to be involved in recruiting these cells into the epidermis in the inflammatory reaction. To address this issue, we investigated whether normal human keratinocytes can produce fractalkine in the presence of cytokines. TNF-□, IL1-□□ and IFN-□ synergistically enhanced IFN-□-induced fractalkine production in normal human keratinocytes. In conclusion, this is the first report showing that normal human keratinocytes produce soluble fractalkine protein.