Jacob S E, Berman B, Nassiri M, Vincek V
Department of Dermatology and Cutaneous Surgery, University of Miami, 1600 NW 10th Ave, Room 2023 A, Miami, FL 33138, USA.
Br J Dermatol. 2003 Nov;149 Suppl 66:62-5. doi: 10.1046/j.0366-077x.2003.05636.x.
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.
瘢痕疙瘩是良性间充质肿瘤，通常出现在既往损伤部位并超出其边缘。据报道，瘢痕疙瘩显示凋亡基因的异常表达：转化生长因子β1（TGFB1）被激活，而半胱天冬酶8和3未被激活，这表明瘢痕疙瘩的凋亡级联反应上游存在阻断。干扰素α2b可使瘢痕疙瘩成纤维细胞过度合成的胶原蛋白、糖胺聚糖和胶原酶正常化，减少瘢痕疙瘩切除后的复发，并增强天然p53的表达和凋亡。咪喹莫特是一种在皮肤应用部位局部快速且强效诱导干扰素的药物，可减少瘢痕疙瘩切除后的复发，并改变基底细胞癌细胞凋亡标志物的基因表达。我们研究了局部应用5%咪喹莫特乳膏治疗瘢痕疙瘩相对于未治疗对照在瘢痕疙瘩组织中凋亡基因表达方面的影响。从切除的瘢痕疙瘩组织中提取总RNA，合成cDNA探针，然后与点在膜上的基因特异性cDNA片段杂交。在咪喹莫特治疗组和未治疗组中，比较了96个参与凋亡的基因相对于亲环蛋白表达的表达水平。半胱天冬酶3和DNA片段化因子α（DFFA）相对于亲环蛋白的平均表达比率显著提高。与未治疗的瘢痕疙瘩组相比，咪喹莫特治疗的瘢痕疙瘩组中半胱天冬酶3显著下调，DFFA显著上调（P < 0.05）。尽管咪喹莫特能够改变瘢痕疙瘩中这些凋亡标志物的表达，但其在瘢痕疙瘩对咪喹莫特治疗反应中的作用（如果有）仍需进一步研究。
