摘要
Background:Actinic keratoses (AKs) are premalignant lesions that can progress into squamous cell carcinoma. Imiquimod, which belongs to the new class of immu ne-response modifiers, was recently shown to be effective in the treatment of A Ks. The underlying mechanisms are not fully understood. Objectives:To study the expression of individual genes in uninvolved skin and AKs before therapy and to elucidate the way in which the expression of these genes is influenced by imiqu imod therapy. Methods:We treated 13 patients with AK with imiquimod and compare d gene expression before, during (five patients) and after (eight patients) ther apy with that in uninvolved skin. We analysed genes coding for inflammatory cyto kines or their receptors, adhesion molecules, anti-apoptotic proteins, p53 and toll-like receptors (TLRs) by reverse-transcriptase polymerase chain reaction. Results:Comparing uninvolved skin and untreatedAK,we found significant differe nces in the expression of interleukin (IL)-6, hurpin, TLR7 and TLR8. During imi quimod therapy, we detected a further upregulation of interferon-α,IL6, IL-10 receptor 1 and TLR7. In contrast, two antiapoptotic genes, hurpin and HAX-1, w ere downregulated. We did not detect significant differences in gene expression for p53, tumour necrosis factor-αand β-catenins. Clinically, the upregulated expression of the proinflammatory cytokines correlated with the local inflammat ion induced by imiquimod. Conclusions:Our results indicate that specific differ ences in gene expression are detectable between AK and uninvolved skin. Imiquimo d influenced the expression of most genes analysed in this study. This work exte nds previous findings on the effects of imiquimod on gene regulation in AKs.
Background:Actinic keratoses (AKs) are premalignant lesions that can progress into squamous cell carcinoma. Imiquimod, which belongs to the new class of immu ne-response modifiers, was recently shown to be effective in the treatment of A Ks. The underlying mechanisms are not fully understood. Objectives:To study the expression of individual genes in uninvolved skin and AKs before therapy and to elucidate the way in which the expression of these genes is influenced by imiqu imod therapy. Methods:We treated 13 patients with AK with imiquimod and compare d gene expression before, during (five patients) and after (eight patients) ther apy with that in uninvolved skin. We analysed genes coding for inflammatory cyto kines or their receptors, adhesion molecules, anti-apoptotic proteins, p53 and toll-like receptors (TLRs) by reverse-transcriptase polymerase chain reaction. Results:Comparing uninvolved skin and untreatedAK,we found significant differe nces in the expression of interleukin (IL)-6, hurpin, TLR7 and TLR8. During imi quimod therapy, we detected a further upregulation of interferon-α,IL6, IL-10 receptor 1 and TLR7. In contrast, two antiapoptotic genes, hurpin and HAX-1, w ere downregulated. We did not detect significant differences in gene expression for p53, tumour necrosis factor-αand β-catenins. Clinically, the upregulated expression of the proinflammatory cytokines correlated with the local inflammat ion induced by imiquimod. Conclusions:Our results indicate that specific differ ences in gene expression are detectable between AK and uninvolved skin. Imiquimo d influenced the expression of most genes analysed in this study. This work exte nds previous findings on the effects of imiquimod on gene regulation in AKs.
