THE CXC RECEPTOR-2 IS OVEREXPRESSED IN PSORIATIC EPIDERMIS

The CXC chemokines interleukin-8 and GRO/melanoma growth-stimulatory a ctivity (GRO-alpha) are potent activators of neutrophils and lymphocyt es, but also stimulate growth and differentiation of nonhematopoietic cells like keratinocytes, fibroblasts, and melanocytes. High mRNA and protein levels have been detected in psoriatic epidermis. Chemokine ac tivation of target cells is mediated by specific receptors and two CXC receptors have been described with similar affinity for interleukin-8 but different affinities for GRO-alpha, In this study, we examined th e expression of both CXCR1 and CXCR2 in psoriatic tissue, identifying the target cells of chemokine activation in psoriasis. By immunohistoc hemistry and in situ hybridization, as confirmed by northern blot anal ysis and reverse transcriptase polymerase chain reaction, we could det ect expression of the CXCR2 in suprabasal lesional psoriatic keratinoc ytes but not in healthy skin. The CXCR1 could not be localized in psor iatic keratinocytes with immunohistochemistry and in situ hybridizatio n, but infiltrating cells in the dermal compartment expressed both typ es of receptors. These data suggest that in addition to neutrophil act ivation by both CXCR1 and CXCR2, activation of keratinocytes mediated by CXCR2 could contribute to the characteristic epidermal changes obse rved in psoriasis.