Nirodi C S, Devalaraja R, Nanney L B, Arrindell S, Russell S, Trupin J, Richmond A
Department of Veterans Affairs, Departments of Cell Biologyand Plastic Surgery, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
Wound Repair Regen. 2000 Sep-Oct;8(5):371-82. doi: 10.1111/j.1524-475x.2000.00371.x.
Keloids are benign collagenous tumors that occur during dermal wound healing in genetically predisposed individuals. The lesions are characterized by over-proliferation of fibroblasts, some leukocyte infiltration, and prolonged high rates of collagen synthesis. To determine whether leukocyte chemoattractants or chemokines are participating in this disease process, immunohistochemical staining for the CXC chemokine, MGSA/GROalpha, and its receptor, CXCR2, was performed on tissue from keloids, hypertrophic scars and normal skin. Immunoreactive MGSA/GROalpha was not observed in hypertrophic scars or normal dermis, but was present in some myofibroblasts and lymphocytes in nodular areas of the keloid samples. This staining positively correlated with the degree of inflammatory infiltrate in the lesions. Keloids, but not hypertrophic scars or normal dermis, also exhibited intensive immunoreactivity for the CXCR2 receptor in endothelial cells and inflammatory infiltrates with occasional staining of myofibroblasts. In contrast, cultured fibroblasts from either keloids or normal skin did not express detectable amounts of mRNA for MGSA/GRO or CXCR2, although interleukin-1 strongly induced MGSA/GRO mRNA in both cell types. Interleukin-1 induction of MGSA/GRO was inhibited by glucocorticoid in normal and keloid fibroblasts, and the effect was more pronounced in keloid fibroblasts. This event was not correlated with inhibition of nuclear activation of NF-kappaB, AP-1 or Sp1, and might therefore be mediated by another mechanism such as decreased mRNA stability or transcriptional repression through the glucocorticoid response element in the MGSA/GRO promoter. Data from in vitro wounding experiments with cultured normal and keloid fibroblasts indicate that there were no significant differences in MGSA/GRO or CXCR2 receptor levels between normal and keloid fibroblasts. We also show that cultured keloid fibroblasts exhibit a delayed wound healing response. We postulate that the inflammatory component is important in development of keloid lesions and chemotactic cytokines may participate in this process.
瘢痕疙瘩是一种良性胶原性肿瘤，发生于具有遗传易感性个体的皮肤伤口愈合过程中。这些病变的特征是成纤维细胞过度增殖、有一些白细胞浸润以及胶原合成速率长期居高不下。为了确定白细胞趋化因子或趋化因子是否参与了这一疾病过程，对瘢痕疙瘩、增生性瘢痕和正常皮肤组织进行了CXC趋化因子MGSA/GROα及其受体CXCR2的免疫组织化学染色。在增生性瘢痕或正常真皮中未观察到免疫反应性MGSA/GROα，但在瘢痕疙瘩样本的结节区域的一些肌成纤维细胞和淋巴细胞中存在。这种染色与病变中的炎症浸润程度呈正相关。瘢痕疙瘩而非增生性瘢痕或正常真皮，在内皮细胞和炎症浸润中也表现出对CXCR2受体的强烈免疫反应性，偶尔肌成纤维细胞也有染色。相比之下，来自瘢痕疙瘩或正常皮肤的培养成纤维细胞未表达可检测量的MGSA/GRO或CXCR2 mRNA，尽管白细胞介素-1在两种细胞类型中均强烈诱导MGSA/GRO mRNA。在正常和瘢痕疙瘩成纤维细胞中，糖皮质激素抑制白细胞介素-1对MGSA/GRO的诱导，且在瘢痕疙瘩成纤维细胞中作用更明显。这一事件与NF-κB、AP-1或Sp1的核激活抑制无关，因此可能由另一种机制介导，如通过MGSA/GRO启动子中的糖皮质激素反应元件降低mRNA稳定性或转录抑制。来自培养的正常和瘢痕疙瘩成纤维细胞的体外创伤实验数据表明，正常和瘢痕疙瘩成纤维细胞之间的MGSA/GRO或CXCR2受体水平没有显著差异。我们还表明，培养的瘢痕疙瘩成纤维细胞表现出延迟的伤口愈合反应。我们推测炎症成分在瘢痕疙瘩病变的发展中很重要，趋化细胞因子可能参与了这一过程。
