Ethanol and acetone stimulate the proliferation of HaCaT keratinocytes: the possible role of alcohol in exacerbating psoriasis.
Alcohol has been reported to be a risk factor in psoriasis mainly based on the observation that there is a higher prevalence of alcohol abuse in individuals with psoriasis. The mechanism by which alcohol affects this disease is still elusive. So far there are no reports describing the effects of metabolites relevant to alcohol metabolism on the growth of human keratinocytes. In the present study we examined the effects of ethanol and acetone, which exceeds its normal endogenous level in the blood of heavy drinkers, on the proliferation of HaCaT keratinocytes. HaCaT cells were incubated for 30 min in the presence of various concentrations of ethanol (2.14 m M-1.71 M) and acetone (1.7 mM-1.36 M). The numbers of viable and proliferating cells were determined at different times after ethanol and acetone treatment. The effects of ethanol and acetone on the mRNA levels of genes characteristic for proliferating keratinocytes such as alpha5 integrin, keratinocyte growth factor receptor and cyclin D1 were studied by reverse-transcriptase polymerase chain reaction. Both ethanol and acetone induced proliferation of HaCaT cells. The maximum increase in the number of viable cells and the maximum proliferative response was observed with 4.28 m M ethanol and 13.6 m M acetone. The alpha5 integrin, keratinocyte growth factor receptor and cyclin D1 mRNA levels were higher compared to the controls as early as 2 h after ethanol and 30 min after acetone treatment of the cells. The stimulatory effect of ethanol and acetone on human keratinocytes may be one of the reasons why psoriasis can be precipitated by alcohol misuse.
Department of Dermatology and Allergology, Faculty of General Medicine, University of Szeged, PO Box 427, H-6701, Szeged, Hungary. farkas@derma.szote.u-szeged.hu
Arpád
A
Farkas
Lajos
L
Kemény
Márta
M
Széll
Attila
A
Dobozy
Zsuzsanna
Z
Bata-Csörgo
D000096:Acetone / Q000494:pharmacology*; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D002461:Cell Line, Transformed; D002470:Cell Survival / Q000187:drug effects; D019938:Cyclin D1 / Q000235:genetics; D000431:Ethanol / Q000494:pharmacology*; D006801:Humans; D039482:Integrin alpha5 / Q000235:genetics; D015603:Keratinocytes / Q000166:cytology* / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D051497:Receptor, Fibroblast Growth Factor, Type 2; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics; D012997:Solvents / Q000494:pharmacology*
D039482:Integrin alpha5; D012333:RNA, Messenger; D017468:Receptors, Fibroblast Growth Factor; D012997:Solvents; D000096:Acetone; D019938:Cyclin D1; D000431:Ethanol; D051497:Receptor, Fibroblast Growth Factor, Type 2; C065104:keratinocyte growth factor receptor