Topical application of imiquimod 5% cream to keloids alters expression genes associated with apoptosis

Br J Dermatol. 2003 Nov:149 Suppl 66:62-5. doi: 10.1046/j.0366-077x.2003.05636.x.

Abstract

Keloids are benign mesenchymal tumours, usually present at and extending beyond the margins of sites of previous injury. It is reported that keloids display aberrant expression of apoptotic genes: TGFB1 is activated, whereas caspase 8 and 3 are not, thus indicating a block upstream in the apoptosis cascade in keloids. Interferon-alpha 2b normalizes the excessive synthesis of collagen, glycosaminoglycans and collagenase by keloidal fibroblasts, reduces recurrences following keloid excision, and enhances the expression of native p53 and apoptosis. Imiquimod, a rapid and potent inducer of interferons locally at the site of application to the skin, reduces recurrences following keloid excision and alters gene expression of markers of apoptosis in basal cell carcinoma cells. We investigated the effects with respect to the expression of apoptotic genes in keloidal tissue compared with nontreated controls of imiquimod 5% cream applied topically to keloids. Total RNA was extracted from excised keloidal tissue, cDNA probes synthesized and then hybridized to gene-specific cDNA fragments spotted on membranes. The expression levels of 96 genes involved in apoptosis, relative to cyclophilin expression, were compared in the imiquimod-treated and untreated groups. The mean ratio of expression, relative to cyclophilin of caspase 3 and DFFA were significantly enhanced. Caspase 3 was significantly downregulated and DFFA was significantly upregulated in the group of imiquimod-treated keloids (P < 0.05) compared with the untreated group of keloids. Although imiquimod is capable of altering the expression of these markers of apoptosis in keloids, their role, if any, in the therapeutic response of keloids to imiquimod requires further investigation.

MeSH terms

  • Adjuvants, Immunologic / therapeutic use*
  • Administration, Topical
  • Aminoquinolines / therapeutic use*
  • Apoptosis
  • Arabidopsis Proteins / genetics
  • Caspase 3
  • Caspase 6
  • Caspase 8
  • Caspases / genetics
  • Drug Administration Schedule
  • Fatty Acid Desaturases / genetics
  • Gene Expression / drug effects
  • Humans
  • Imiquimod
  • Keloid / drug therapy*
  • Keloid / pathology
  • Lymphotoxin-alpha / genetics

Substances

  • Adjuvants, Immunologic
  • Aminoquinolines
  • Arabidopsis Proteins
  • Lymphotoxin-alpha
  • Fatty Acid Desaturases
  • Fad7 protein, Arabidopsis
  • CASP3 protein, human
  • CASP6 protein, human
  • CASP8 protein, human
  • Caspase 3
  • Caspase 6
  • Caspase 8
  • Caspases
  • Imiquimod