Harrisburg and Hershey, Pa. From Leber & Wolf Plastic Surgery Limited; and the Division of Plastic Surgery, Department of Surgery, The Pennsylvania State University, College of Medicine.
Plast Reconstr Surg. 2014 May;133(5):638e-644e. doi: 10.1097/PRS.0000000000000103.
Dexamethasone, a common therapy for reducing hypertrophic scar, sometimes fails. However, in cell culture, all dexamethasone-treated fibroblasts die. In co-cultures, gap junction intercellular communications between mast cells and fibroblasts promote profibrotic activities. Does the co-culture of mast cells with fibroblasts prevent dexamethasone-induced fibroblast death?
Survival of fibroblasts co-cultured with RMC-1 cells, a rat mast cell line, receiving dexamethasone was studied. RMC-1 cells pretreated with a secretagogue that degranulated mast cells and/or with a long-acting gap junction intercellular communications inhibitor were compared to untreated RMC-1 cells co-cultured with fibroblasts and dexamethasone.
Fibroblasts alone treated with dexamethasone all died in 3 hours. Fibroblasts co-cultured with intact RMC-1 cells or with degranulated RMC-1 cells in dexamethasone all survived. No fibroblasts survived, co-cultured with RMC-1 cells unable to form gap junction intercellular communications with fibroblasts.
Dexamethasone-treated fibroblasts, forming gap junction intercellular communications with mast cells, may explain why dexamethasone therapy sometimes fails. Gap junction intercellular communications between scar mast cells and fibroblasts or myofibroblasts apparently blocks the death of these cell populations. Preventing gap junction intercellular communications between mast cells and fibroblasts by including anti-gap junction intercellular communication agents may enhance the effectiveness of steroid therapy in treating excessive scarring.
地塞米松是一种常用于减少增生性瘢痕的治疗方法，但有时会失败。然而，在细胞培养中，所有接受地塞米松治疗的成纤维细胞都会死亡。在共培养中，肥大细胞和成纤维细胞之间的缝隙连接细胞间通讯促进了致纤维化活性。肥大细胞与成纤维细胞的共培养是否能防止地塞米松诱导的成纤维细胞死亡？
研究了与大鼠肥大细胞系 RMC-1 共培养的成纤维细胞在接受地塞米松后是否存活。将预先用脱颗粒肥大细胞的 secretagogue 或长效缝隙连接细胞间通讯抑制剂处理的 RMC-1 细胞与未经处理的 RMC-1 细胞共培养，并与接受地塞米松治疗的成纤维细胞进行比较。
单独用地塞米松处理的成纤维细胞在 3 小时内全部死亡。与完整的 RMC-1 细胞或与脱颗粒的 RMC-1 细胞共培养的成纤维细胞在接受地塞米松治疗后均存活。与无法与成纤维细胞形成缝隙连接细胞间通讯的 RMC-1 细胞共培养的成纤维细胞均未存活。
与肥大细胞形成缝隙连接细胞间通讯的地塞米松处理的成纤维细胞可能解释了为什么地塞米松治疗有时会失败。瘢痕肥大细胞和成纤维细胞或肌成纤维细胞之间的缝隙连接细胞间通讯显然阻止了这些细胞群体的死亡。通过包括抗缝隙连接细胞间通讯剂来阻止肥大细胞和成纤维细胞之间的缝隙连接细胞间通讯，可能会增强类固醇治疗治疗过度瘢痕形成的有效性。
