The Herpes simplex virus gene Pol expressed in herpes-associated erythema multiforme lesions upregulates/activates SP1 and inflammatory cytokines

Dermatology. 2007;215(2):97-106. doi: 10.1159/000104259.

Abstract

Background/aims: Herpes-simplex-virus-associated erythema multiforme (HAEM) is characterized by lesional skin expression of the viral protein Pol and localized inflammation. The objective of this study is to examine the mechanism whereby Pol induces localized inflammation.

Methods: A431 cells transfected with Pol or an empty vector and lesional skin from HAEM or drug-induced erythema multiforme patients were examined for expression of the transcription factor SP1 and SP1-regulated genes by immunoblotting, immunohistochemistry and immunofluorescence.

Results: SP1, TGF-beta, p21(waf1) and Hsp27 were upregulated in A431 cells transfected with Pol but not the empty vector. Expression was further increased by exposure to IFN-gamma. Pol+ HAEM lesional skin expressed SP1, Hsp27, TGF-beta and p21(waf1). Normal skin and drug-induced erythema multiforme lesional skin were negative.

Conclusion: The data indicate that Pol activates SP1, causing upregulation of SP1 target genes (notably TGF-beta) involved in localized inflammation. Upregulation is potentiated by IFN-gamma.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • Cytokines / metabolism
  • Drug Eruptions / genetics
  • Drug Eruptions / pathology
  • Erythema Multiforme / etiology
  • Erythema Multiforme / genetics*
  • Erythema Multiforme / pathology
  • Genes, pol / physiology*
  • Humans
  • Immunoblotting
  • Inflammation / etiology
  • Inflammation / genetics*
  • Inflammation / metabolism
  • Interferon-gamma / metabolism
  • Intracellular Signaling Peptides and Proteins
  • Keratinocytes / metabolism
  • Protein Serine-Threonine Kinases / metabolism
  • Simplexvirus / genetics*
  • Simplexvirus / metabolism
  • Sp1 Transcription Factor / genetics
  • Sp1 Transcription Factor / metabolism*
  • Transfection
  • Transforming Growth Factor beta / metabolism
  • Up-Regulation

Substances

  • Cyclin-Dependent Kinase Inhibitor p21
  • Cytokines
  • Intracellular Signaling Peptides and Proteins
  • Sp1 Transcription Factor
  • Transforming Growth Factor beta
  • Interferon-gamma
  • MAP-kinase-activated kinase 2
  • Protein Serine-Threonine Kinases