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


CONCLUSIONS
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.
Gober
Michael D
MD
Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore, MD 21201-1559, USA.
Laing
Jennifer M
JM
Burnett
Joseph W
JW
Aurelian
Laure
L
D000328:Adult; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003875:Drug Eruptions / Q000235:genetics / Q000473:pathology; D004892:Erythema Multiforme / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D015751:Genes, pol / Q000502:physiology*; D006801:Humans; D015151:Immunoblotting; D007249:Inflammation / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D015603:Keratinocytes / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D018139:Simplexvirus / Q000235:genetics* / Q000378:metabolism; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000378:metabolism; D015854:Up-Regulation; D000099190:MAP-Kinase-Activated Kinase 2
D050759:Cyclin-Dependent Kinase Inhibitor p21; D016207:Cytokines; D007371:Interferon-gamma; D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases; D016329:Sp1 Transcription Factor; D016212:Transforming Growth Factor beta; D000099190:MAP-Kinase-Activated Kinase 2