Kondo S, Yoneta A, Yazawa H, Kamada A, Jimbow K
Department of Dermatology, Faculty of Medicine, Sapporo Medical University, Sapporo, Japan.
J Cell Physiol. 2000 Mar;182(3):366-70. doi: 10.1002/(SICI)1097-4652(200003)182:3<366::AID-JCP7>3.0.CO;2-8.
Interleukin-8 (IL-8) belongs to the CXC chemokine family. IL-8 exerts its biological activities by binding to specific cell surface receptors, CXCR-1 and CXCR-2. Both receptors bind IL-8 with high affinity but they have different affinities for MGSA/Groalpha and NAP-2. It has been shown that the expression of epidermal CXCR-2 is increased in psoriasis, suggesting that activation of KC mediated by CXCR-2 contributes to the characteristic epidermal changes observed in psoriasis. In order to examine the mechanism(s) by which UVB therapy is effective for several dermatoses including psoriasis, we sought to examine if UVB would modulate the expression of CXCR-1 and CXCR-2 in human keratinocytes (KC). Constitutive expression of CXCR-1 and CXCR-2 mRNA was detected by RT-PCR in normal cultured human KC. After 100 or 300 J/m(2) irradiation, a decrease in CXCR-2 mRNA was detectable from 12 h after irradiation; this downregulation was observed until 48 h after irradiation. In contrast, the CXCR-1 mRNA level was unchanged. Immunohistochemical studies and flow cytometry analysis confirmed the suppressive effect of UVB on the expression of CXCR-2 protein in cultured human keratinocytes. Immunohistochemical studies on two minimal erythema doses (2MED)-exposed and 2MED-unexposed skin from healthy volunteers revealed that CXCR-2 staining occurred over the whole layer of the epidermis but at 24 h after 2MED irradiation, the positive staining of CXCR-2 was decreased. A faint CXCR-1 staining was observed in the lower part of the epidermis both in unexposed and exposed skins. Our results indicate that UVB-induced growth inhibition of KC in hyperproliferative skin disorders may, in part, be related to downregulation of CXCR-2.
白细胞介素-8（IL-8）属于CXC趋化因子家族。IL-8通过与特定的细胞表面受体CXCR-1和CXCR-2结合来发挥其生物学活性。这两种受体都以高亲和力结合IL-8，但它们对MGSA/Groα和NAP-2的亲和力不同。研究表明，银屑病患者表皮CXCR-2的表达增加，提示CXCR-2介导的角质形成细胞（KC）活化促成了银屑病中观察到的特征性表皮变化。为了研究紫外线B（UVB）疗法对包括银屑病在内的几种皮肤病有效的机制，我们试图检测UVB是否会调节人角质形成细胞（KC）中CXCR-1和CXCR-2的表达。通过逆转录聚合酶链反应（RT-PCR）在正常培养的人KC中检测到CXCR-1和CXCR-2 mRNA的组成性表达。在100或300 J/m²照射后，照射后12小时可检测到CXCR-2 mRNA减少；这种下调一直持续到照射后48小时。相比之下，CXCR-1 mRNA水平未改变。免疫组织化学研究和流式细胞术分析证实了UVB对培养的人角质形成细胞中CXCR-2蛋白表达的抑制作用。对健康志愿者暴露于两个最小红斑量（2MED）和未暴露于2MED的皮肤进行的免疫组织化学研究表明，CXCR-2染色出现在表皮全层，但在2MED照射后24小时，CXCR-2的阳性染色减少。在未暴露和暴露皮肤的表皮下部均观察到微弱的CXCR-1染色。我们的结果表明，UVB诱导的增生性皮肤病中KC生长抑制可能部分与CXCR-2的下调有关。
