In:
Pathobiology, S. Karger AG, Vol. 68, No. 6 ( 2000), p. 291-300
Abstract:
〈 i 〉 Objective: 〈 /i 〉 Lichen planus (LP) represents a disease in which autoimmune mechanisms mediated by Th1 T cells are involved. Lymphotoxin-α (LT-α) represents a Th1 cytokine with proinflammatory activities in LP, as has recently been demonstrated for interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α). 〈 i 〉 Methods: 〈 /i 〉 Expression of LT-α mRNA was investigated by RT-PCR and nonradioactive in situ hybridization. Double staining methods were applied to characterize the phenotype of cells expressing LT-α. Cell stimulation experiments were performed on the transformed squamous cell line HaCaT. 〈 i 〉 Results: 〈 /i 〉 In contrast to normal skin, LT-α-specific RT-PCR products were found in all cases of LP. Cells in the inflammatory infiltrate expressing LT-α were identified as mainly T cells and mast cells, as shown by in situ hybridization. Furthermore, predominant LT-α mRNA expression could be observed in lesional keratinocytes adjacent to the band-like inflammatory infiltrate. In cell stimulation experiments, it could be shown that IFN-γ induces LT-α and TNF-α mRNA in the human squamous cell line HaCaT, concomitant with upregulation of MHC class II and intercellular adhesion molecule-1, which could also be observed on lesional keratinocytes in LP. 〈 i 〉 Conclusions: 〈 /i 〉 In LP, LT-α mRNA is predominantly expressed by lesional keratinocytes and to a lesser extent by inflammatory cells. Induction of LT-α in keratinocytes is closely related to the expression of TNF-α and MHC class II. The loci of TNF-α and LT-α map to MHC class III on chromosome 6, which is closely linked to the MHC class II gene locus. Our results suggest that stimulation of keratinocytes with IFN-γ results in the upregulation of proinflammatory cytokines such as LT-α and TNF-α as well as MHC class II, which map to the same gene region of immunoregulatory genes on chromosome 6 and may be involved in the induction and maintenance of the disease.
Type of Medium:
Online Resource
ISSN:
1015-2008
,
1423-0291
Language:
English
Publisher:
S. Karger AG
Publication Date:
2000
detail.hit.zdb_id:
1483541-1
SSG:
12
Bookmarklink