Study of IFNgamma-induced interleukin 8, ICAM-1 and HLA-DR expression in various models of reconstructed skin: Comparison with normal human skin in short-term organ culture

Many inflammatory skin diseases are associated with leucocyte infiltrates, keratinocyte expression of HLA-DR or ICAM-1, and production of various chemotaxins (IL-8, MCAF). Most studies concerning keratinocyte activation by leucocyte derived factors (e.g. IFNgamma) have been performed on conventional monolayer cultures. As interactions with matrix or other cells, or differentiation stage may be of importance in keratinocyte responses, we decide to use various systems of reconstructed epidermis to address this issue. Our results demonstrate that the expression and distribution of ICAM-1 and HLA-DR (two surface antigens involved in keratinocyte/lymphocyte interactions) by IFNgamma-treated reconstructed epidermis is similar to that obtained under identical conditions using normal human skin, and to human skin intradermally injected with IFNgamma. Reconstructed epidermis is also able to release the potent leucocyte chemotaxin IL-8 in response to IFN-gamma stimulation. Comparisons between different models of reconstructed epidermis did not reveal any marked influence of matrix or other skin cells upon ICAM-1 and HLA-DR expression by keratinocytes. These comparisons also showed that IL-8 was predominantly produced by fibroblasts present in the dermal equivalent, although epidermal keratinocytes were able to produce low, but significant levels of this cytokine. Neither synergistic nor antagonistic mechanisms seemed to operate between these two cell types as regards IFNgamma-stimulated IL-8 production. The variety of models of reconstructed epidermis makes this approach a powerful and versatile in vitro tool for the investigation of keratinocyte responses during immunological and inflammatory processes at the tissue level.