细胞信号传导在激素和干扰素诱导的增殖瘢痕成纤维细胞凋亡中的作用

目的 探讨对瘢痕疙瘩和增生性瘢痕成纤维细胞在激素和干扰素α-2b(IFNα-2b)作用后是否产生凋亡,以及相关细胞信号传导通路的激活或抑制是否一致.方法 对6例瘢痕疙瘩、增生性瘢痕及6例皮肤标本,采用细胞培养、免疫组织化学、凝胶电泳及FACE ELISA方法通过检测Bax和Bcl-2蛋白表达、特异性DNA梯状条带以及激活(磷酸化)的ERK1/2和JNK的吸光度A值,对不同成纤维细胞在地塞米松(0.1 mg/ml)和干扰素α-2b(1000U/ml)作用后的细胞凋亡及相关细胞信号传导通路进行了研究.结果 地塞米松可通过激活ERK1/2和JNK细胞传导通路诱导三类不同来源成纤维细胞发生细胞凋亡;干扰素α-2b不能诱导这三类不同来源成纤维细胞发生明显细胞凋亡,且IFN α-2b抑制增殖瘢痕的ERK1/2通路,而对JNK通路无影响,其不引起正常皮肤成纤维细胞ERK1/2和JNK通路的变化.结论 激素类药物和干扰素α-2b对瘢痕疙瘩、增生性瘢痕和正常皮肤成纤维细胞的作用机制不同.

The role of cell pathway in apoptosis of fibroblasts from proliferative scar induced by steroid or IFN

OBJECTIVE: This paper is to investigate the effects of steroid or IFN alpha-2b on apoptosis and cell pathway of fibroblasts from keloids, hypertrophic scars and normal skins and different responses of different fibroblasts. METHODS: 6 samples from keloid, hypertrophic scar and normal skin were collected respectively and fibroblasts from different sources were cultured in vitro. After different fibroblasts were treated with dexamethasone (0.1 mg/ml) or IFN alpha-2b (1000 U/ml), Bax and Bcl-2 protein expressions were detected in situ by immunohistochemical staining; DNA ladders of different fibroblasts were observed by gel electrophoresis; and relative activated (phospho-) ERK1/2 and JNK pathways were detected by method of FACE ELISA. RESULTS: Dexamethasone could induce apoptosis of fibroblasts from keloids, hypertrophic scars and normal skins through activating (phospho-) ERK1/2 and JNK pathways; IFN alpha-2b could not induce apoptosis of fibroblasts from different sources. IFN alpha-2b could inhibit (phospho-) ERK1/2 pathway and could not affect (phospho-) JNK pathways of fibroblasts from keloid and hypertrophic scar. IFN alpha-2b could affect neither (phospho-) ERK1/2 pathway nor (phospho-) JNK pathways of fibroblasts from normal skin. CONCLUSIONS: The responses of different fibroblasts to steroid or IFN alpha-2b were different.