Downregulation of CXCR-2 but not CXCR-1 expression by human keratinocytes by UVB

Interleukin-8 (IL-8) belongs to the CXC chemokine family. IL-8 exerts its b iological activities by binding to specific cell surface receptors, CXCR-1 and CXCR-2. Both receptors bind IL-8 with high affinity but they have diffe rent affinities for MGSA/Gro alpha and NAP-2. It has been shown that the ex pression of epidermal CXCR-2 is increased in psoriasis, suggesting that act ivation of KC mediated by CXCR-2 contributes to the characteristic epiderma l changes observed in psoriasis. In order to examine the mechanism(s) by wh ich 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 afte r irradiation; this downregulation was observed until 48 h after irradiatio n. In contrast, the CXCR-1 mRNA level was unchanged. Immunohistochemical st udies and flow cytometry analysis confirmed the suppressive effect of UVB o n the expression of CXCR-2 protein in cultured human keratinocytes. Immunoh istochemical studies on two minimal erythema doses (2MED)-exposed and 2MED- unexposed skin from healthy volunteers revealed that CXCR-2 staining occurr ed 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 wa s 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 hy perproliferative skin disorders may, in part, be related to downregulation of CXCR-2. (C) 2000 Wiley-Liss, Inc.