title: Expression of lymphotoxin-alpha by keratinocytes: a further mediator for the lichenoid reaction.
abstract: OBJECTIVE
  Lichen planus (LP) represents a disease in which autoimmune mechanisms mediated by Th1 T cells are involved. Lymphotoxin-alpha (LT-alpha) represents a Th1 cytokine with proinflammatory activities in LP, as has recently been demonstrated for interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha).
  
  
  METHODS
  Expression of LT-alpha mRNA was investigated by RT-PCR and nonradioactive in situ hybridization. Double staining methods were applied to characterize the phenotype of cells expressing LT-alpha. Cell stimulation experiments were performed on the transformed squamous cell line HaCaT.
  
  
  RESULTS
  In contrast to normal skin, LT-alpha-specific RT-PCR products were found in all cases of LP. Cells in the inflammatory infiltrate expressing LT-alpha were identified as mainly T cells and mast cells, as shown by in situ hybridization. Furthermore, predominant LT-alpha 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-gamma induces LT-alpha and TNF-alpha 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.
  
  
  CONCLUSIONS
  In LP, LT-alpha mRNA is predominantly expressed by lesional keratinocytes and to a lesser extent by inflammatory cells. Induction of LT-alpha in keratinocytes is closely related to the expression of TNF-alpha and MHC class II. The loci of TNF-alpha and LT-alpha 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-gamma results in the upregulation of proinflammatory cytokines such as LT-alpha and TNF-alpha 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.
authors.affiliation: Department of Pathology, Georg August University of Göttingen, Robert-Koch-Strasse 40, D-37073 Göttingen, Germany. pmiddel@med.uni-goettingen.de
authors.forename: P
authors.initials: P
authors.lastname: Middel
authors.forename: U
authors.initials: U
authors.lastname: Lippert
authors.forename: K M
authors.initials: KM
authors.lastname: Hummel
authors.forename: H P
authors.initials: HP
authors.lastname: Bertsch
authors.forename: M
authors.initials: M
authors.lastname: Artuc
authors.forename: S
authors.initials: S
authors.lastname: Schweyer
authors.forename: H J
authors.initials: HJ
authors.lastname: Radzun
mesh_terms: D002461:Cell Line, Transformed; D017931:DNA Primers / Q000737:chemistry; D006684:HLA-DR Antigens / Q000096:biosynthesis; D006801:Humans; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D007371:Interferon-gamma / Q000494:pharmacology; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008010:Lichen Planus / Q000378:metabolism* / Q000473:pathology; D008233:Lymphotoxin-alpha / Q000096:biosynthesis* / Q000235:genetics; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology
chemical_list: D017931:DNA Primers; D006684:HLA-DR Antigens; D008233:Lymphotoxin-alpha; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma