11180008

pubmed:Citation

2

SUMMARY: Psoriasis is a chronic skin disease with an immunocytic infiltrate, including activated T lymphocytes, producing multiple cytokines that can influence the phenotype of epidermal keratinocytes. In these studies we examined the effect of the cytokines interferon-gamma and interleukin-13 or interleukin-4 on keratinocytes, alone and in combination, on surface levels of HLA-DR, intercellular adhesion molecule 1, and CDw60, as well as the transcription factors STAT1, STAT6, and BCL-6. As CDw60 is an acetylated form of the GD3 ganglioside and may function as a T cell costimulatory molecule, the modulation of CDw60 expression by keratinocytes in psoriatic lesions was highlighted to gain insight into potentially important T cell-keratinocyte interactions. Interferon-gamma was observed to block the interleukin-4- or interleukin-13-mediated induction of CDw60 on cultured keratinocytes, but not induction of the transcription factor STAT6. Interleukin-13 and interleukin-4 were unable to block interferon-gamma-mediated induction of STAT1 or BCL-6, however, or the upregulation of intercellular adhesion molecule 1 and HLA-DR. In psoriatic plaques, CDw60 was not consistently detected on keratinocytes in acute lesions, but was detected predominantly on basal layer keratinocytes in chronic lesions. In addition we found that BCL-6 levels were increased in psoriatic lesions; in acute lesions BCL-6 was primarily localized in the basal layer keratinocytes, whereas in chronic plaques nuclear BCL-6 was predominantly expressed by keratinocytes in the suprabasal cell layers. These studies highlight the complex modulation of the keratinocyte phenotype by immunocyte-derived cytokines, in which induction of CDw60 involving interleukin-4, or interleukin-13 was antagonized by interferon-gamma. We suggest in psoriatic plaques that the presence or absence of CDw60 expression by keratinocytes may reflect the dynamic interplay between Th-1-type cytokines such as interferon-gamma and Th-2-type cytokines such as interleukin-4 and interleukin-13. The ability of interferon-gamma to induce the transcription repressor BCL-6 may also contribute to the overall immunologic events in skin, including suppression of the intermediates in the synthetic pathway leading to expression of the T cell costimulatory ganglioside CDw60.

eng

IM

MEDLINE

0022-202X

Print

NLM

305-12

pubmed-meshheading:11180008-Acute Disease, pubmed-meshheading:11180008-Animals, pubmed-meshheading:11180008-Antigens, CD, pubmed-meshheading:11180008-Antigens, Differentiation, T-Lymphocyte, pubmed-meshheading:11180008-Chronic Disease, pubmed-meshheading:11180008-DNA-Binding Proteins, pubmed-meshheading:11180008-Humans, pubmed-meshheading:11180008-Infant, Newborn, pubmed-meshheading:11180008-Interferon-gamma, pubmed-meshheading:11180008-Interleukin-13, pubmed-meshheading:11180008-Interleukin-4, pubmed-meshheading:11180008-Keratinocytes, pubmed-meshheading:11180008-Male, pubmed-meshheading:11180008-Mice, pubmed-meshheading:11180008-Mice, SCID, pubmed-meshheading:11180008-Proto-Oncogene Proteins, pubmed-meshheading:11180008-Proto-Oncogene Proteins c-bcl-6, pubmed-meshheading:11180008-Psoriasis, pubmed-meshheading:11180008-STAT1 Transcription Factor, pubmed-meshheading:11180008-STAT6 Transcription Factor, pubmed-meshheading:11180008-Skin, pubmed-meshheading:11180008-Trans-Activators, pubmed-meshheading:11180008-Transcription Factors

Keratinocyte CDw60 expression is modulated by both a Th-1 type cytokine IFN-gamma and Th-2 cytokines IL-4 and IL-13: relevance to psoriasis.

Journal Article, Research Support, U.S. Gov't, P.H.S.