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.