Human keratinocytes constitutively express IL-4 receptor molecules and respond to IL-4 with an increase in B7/BB1 expression.
In certain pathological conditions, such as atopic dermatitis, interleukin-4 (IL-4) can be detected in the skin. As the role of this cytokine in inflammatory skin lesions is not completely clear, we investigated its biological effects on skin keratinocytes. It was found that freshly isolated as well as cultured keratinocytes obtained from normal individuals express mRNA for the IL-4 receptor (IL-4R) and produce IL-4R protein, as determined by flow cytometry. Moreover, IL-4 induced a proliferative response in keratinocytes after 1 day of culture and enhanced B7/BB1 expression in these cells. B7-2 (CD86) mRNA and protein were neither detected on untreated nor IL-4 treated keratinocytes. In contrast to interferon-gamma (IFN-gamma), IL-4 did not induce ICAM-1 (CD54) or HLA-DR-expression. Keratinocytes which had been treated with IL-4 showed an enhanced ability to stimulate allogeneic T-cell proliferation in the presence of staphylococcus enterotoxin B (SEB), (p < 0.01). Neutralizing anti-B7/BB1 monoclonal antibodies did not block this effect. These results indicate that other molecules than B7/BB-1. HLA-DR or ICAM-1 on IL-4-activated keratinocytes may be involved in T-cell stimulation. In conclusion our results suggest that locally produced IL-4, besides modulating keratinocyte membrane molecules, may enable keratinocytes to interact with skin infiltrating lymphocytes.
Junghans
V
V
Department of Dermatology, University of Göttingen, Germany.
Jung
T
T
Neumann
C
C
D015703:Antigens, CD / Q000096:biosynthesis*; D018122:B7-1 Antigen / Q000096:biosynthesis*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004768:Enterotoxins / Q000494:pharmacology; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology*; D015603:Keratinocytes / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000187:drug effects; D018123:Receptors, Interleukin / Q000096:biosynthesis*; D019948:Receptors, Interleukin-4
D015703:Antigens, CD; D018122:B7-1 Antigen; D004768:Enterotoxins; D006684:HLA-DR Antigens; D018123:Receptors, Interleukin; D019948:Receptors, Interleukin-4; D018799:Intercellular Adhesion Molecule-1; D015847:Interleukin-4; C031818:enterotoxin B, staphylococcal; D007371:Interferon-gamma