Yeh Fa-Lai, Shen Horng-Der, Lin Ming-Wei, Chang Ching-Yun, Tai Hsiao-Yun, Huang Mei-Hsiang
Division of Plastic and Reconstructive Surgery, Department of Surgery, Taipei Veterans General Hospital and National Yang-Ming University, Shih-pai, Taipei, Taiwan 11217, ROC.
Burns. 2006 May;32(3):299-304. doi: 10.1016/j.burns.2005.10.009. Epub 2006 Feb 17.
Keloids result from pathological wound healing responses. However, the pathogenesis of keloids is still poorly understood. PGE2 was shown to decrease fibroblast proliferation, inhibit collagen synthesis and enhance the expression of matrix-metalloproteinases (MMPs). This study sought to delineate the production of PGE2 by normal and keloid-derived dermal fibroblasts. Human normal and keloid dermal fibroblasts were cultured in vitro. Cell proliferation and viability were determined based on WST-1 assay. IL-1beta-induced PGE2 production and effects of PGE2 on the synthesis of procollagen by culture-derived fibroblasts were determined by using enzyme-linked immunosorbant assay (ELISA) kits. IL-1beta-induced MMP-1 production by culture-derived fibroblasts was determined with an MMP-1 immunoassay kit. Our results showed that normal and keloid-derived fibroblasts exhibited a statistically significant increase (p<0.05) in cell proliferation when the cells were cultured in media with an increase in the concentrations (0%, 2% and 10%) of fetal bovine serum (FBS). In culture medium without FBS, an increase in cell proliferation of keloid-derived fibroblasts was detectable when compared with those of control fibroblasts. IL-1beta (1 ng/ml and 10 ng/ml) stimulated statistically significant production (p<0.01) of PGE2 by both normal and keloid-derived fibroblasts. However, lower levels of PGE2 produced by keloid-derived fibroblasts were detectable compared with those produced by normal-derived fibroblasts (p<0.05). In this study, although not statistically significant, inhibition of procollagen production by PGE2 in a dose-dependent manner was found. In addition, decreased production of MMP-1 by keloid-derived fibroblasts compared with those of control fibroblasts was also observed. In conclusion, keloid-derived fibroblasts produced less PGE2 than those produced by control fibroblasts. The role of diminished capacity of PGE2 production in keloid formation is presently unknown and needs further study.
瘢痕疙瘩源于病理性伤口愈合反应。然而,瘢痕疙瘩的发病机制仍未完全明确。前列腺素E2(PGE2)可减少成纤维细胞增殖、抑制胶原蛋白合成并增强基质金属蛋白酶(MMPs)的表达。本研究旨在明确正常及瘢痕疙瘩来源的真皮成纤维细胞中PGE2的产生情况。体外培养人正常及瘢痕疙瘩真皮成纤维细胞。基于WST-1检测法测定细胞增殖和活力。使用酶联免疫吸附测定(ELISA)试剂盒测定白细胞介素-1β(IL-1β)诱导的PGE2产生以及PGE2对培养的成纤维细胞前胶原合成的影响。使用MMP-1免疫测定试剂盒测定培养的成纤维细胞中IL-1β诱导的MMP-1产生。我们的结果显示,当细胞在含有不同浓度(0%、2%和10%)胎牛血清(FBS)的培养基中培养时,正常及瘢痕疙瘩来源的成纤维细胞的细胞增殖均出现统计学显著增加(p<0.05)。在无FBS的培养基中,与对照成纤维细胞相比,瘢痕疙瘩来源的成纤维细胞的细胞增殖有所增加。IL-1β(1 ng/ml和10 ng/ml)刺激正常及瘢痕疙瘩来源的成纤维细胞产生统计学显著水平(p<0.01)的PGE2。然而,与正常来源的成纤维细胞相比,瘢痕疙瘩来源的成纤维细胞产生的PGE2水平较低(p<0.05)。在本研究中,虽然无统计学显著差异,但发现PGE2以剂量依赖方式抑制前胶原产生。此外,与对照成纤维细胞相比,瘢痕疙瘩来源的成纤维细胞产生的MMP-1也减少。总之,瘢痕疙瘩来源的成纤维细胞产生的PGE2比对照成纤维细胞少。PGE2产生能力降低在瘢痕疙瘩形成中的作用目前尚不清楚,需要进一步研究。