Human keratinocytes express fractalkine/CX3CL1.
ABSTRACT fractalkine/CX3CL1 is a unique chemokine that has properties of both chemoattractants and adhesion molecules. The major source of this chemokine in the skin is still controversial.
studies were undertaken to determine the expression of fractalkine in human skin.
RT-PCR, Western blotting, and immunostaining were performed with normal human epidermal keratinocytes (NHEK) and HaCaT cells, human keratinocyte cell line, for the presence of fractalkine. Biopsy specimens of normal and diseased skin were also investigated.
we identified that NHEK and HaCaT cells expressed fractalkine mRNA and protein. The combination of tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma upregulated their expression by NHEK. Immunohistochemistry demonstrated fractalkine expression in keratinocytes in lichen planus and psoriasis vulgaris. RT-PCR also showed that lesional skin of psoriatic patients expressed higher levels of fractalkine mRNA than non-lesional skin from the same patients.
these results suggests that keratinocytes strongly express fractalkine in lichen planus and psoriasis vulgaris and that the fractalkine-CXC3CR1 system in the diseased skin can be a target for the treatment.
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ABSTRACT: Abstract Lichen planus is asumed to represent a delayed hypersensitivity reaction, in the course of which cytokines control the proliferation and differentiation of cytotoxic T lymphocytes which attack the epidermis and cause apoptosis of undifferentiated keratinocytes. Since interferon-γ and interleukin 6 are known to be markedly generated in lichen planus, we investigated the cellular localization of these cytokines in affected skin/oral mucosa biopsy specimens using in situ hybridization for interferon-γ and in situ reverse transcription-polymerase chain reaction for interleukin 6 mRNA. In the upper subepithelial connective tissue interferon-γ mRNA was noted within proliferating CD3+ T lymphocytes. In this tissue compartment interleukin 6 mRNA was detected in infiltrating CD4+ and CD8+ T lymphocytes. In the epithelium, expression of interferon-γ mRNA and interleukin 6 mRNA was observed in the basal and suprabasal keratinocytes of altered skin/oral mucosa. In contrast, normal skin did not reveal any interferon-γ or interleukin 6 expression, although a few CD4+ and CD8+ T lymphocytes were noted in the dermis as well as the epidermis. These findings indicate that in lichen planus the proinflammatory cytokines interferon-γ and interleukin 6 are produced not only by activated T lymphocytes but also by altered keratinocytes, and suggest that stimulated keratinocytes may amplify the course of lichen planus.Archives for Dermatological Research 01/1999; 291(9):485-490. · 2.71 Impact Factor
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ABSTRACT: In normal human epidermis, expression of HLA-DR antigen is restricted to Langerhans cells (LC) and acrosyringial epithelium. However, in diseases such as lichen planus and graft-vs.-host, HLA-DR antigen appears to be expressed by keratinocytes, although the exact source of the HLA-DR is unclear. Two possibilities are that (1) the HLA-DR is shed by neighboring immunocompetent cells, or (2) that the keratinocytes are synthesizing the antigen themselves. Recently, gamma interferon has been shown to induce HLA-DR biosynthesis and expression on human malignant melanoma cells lines and on normal vascular endothelium. We report here that pure recombinant human gamma interferon (100 units/ml) induces HLA-DR expression on 60-70% of cultured human adult keratinocytes depleted of LC within 2-4 days of culture as determined by fluorescence-activated cell sorter (FACS) analysis using monoclonal antibodies. No residual LC or lymphocytes could be detected in these cultures. This is the first demonstration of HLA-DR expression by cultured human keratinocytes. This expression may be of functional significance in antigen presentation and cell-mediated cytotoxicity involving the epidermis.Journal of Investigative Dermatology 09/1984; 83(2):88-90. · 6.19 Impact Factor