Chemokine and chemokine receptor expression in keloid and normal fibroblasts
Chemokine and chemokine receptor expression in keloid and normal fibroblasts
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DOI：
10.1046/j.1524-475x.2000.00371.x
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发表时间：
2000-09-01
影响因子：
2.9
通讯作者：
Richmond, A
中科院分区：
文献类型：
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作者：
Nirodi, CS;Devalaraja, R;Richmond, A
瘢痕疙瘩是一种良性的胶原性肿瘤，发生在遗传易感个体的皮肤伤口愈合过程中。病变的特征是成纤维细胞过度增殖，一些白细胞浸润，和长期的高胶原合成率。为了确定白细胞趋化因子或趋化因子是否参与该疾病过程，对来自瘢痕疙瘩、增生性瘢痕和正常皮肤的组织进行CXC趋化因子MGSA/GRO α及其受体CXCR 2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/GRO α，但在瘢痕疙瘩样本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性浸润程度呈正相关。瘢痕疙瘩，而不是增生性瘢痕或正常真皮，也表现出强烈的免疫反应CXCR 2受体在内皮细胞和炎性浸润肌成纤维细胞偶见染色。与此相反，培养的成纤维细胞无论是瘢痕疙瘩或正常皮肤没有表达可检测量的MGSA/GRO或CXCR 2的mRNA，虽然白细胞介素-1强烈诱导MGSA/GRO mRNA在这两种细胞类型。在正常和瘢痕疙瘩成纤维细胞中，糖皮质激素抑制MGSA/GRO的白细胞介素-1诱导，并且在瘢痕疙瘩成纤维细胞中效果更明显。该事件与NF-κ B、AP-1或Sp1的核活化抑制无关，因此可能由另一种机制介导，例如通过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。用培养的正常和瘢痕疙瘩成纤维细胞进行的体外创伤实验的数据表明，正常和瘢痕疙瘩成纤维细胞之间的MGSA/GRO或CXCR 2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是重要的，趋化性细胞因子可能参与了这一过程。
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/GRO alpha, and its receptor, CXCR2, was performed on tissue from keloids, hypertrophic scars and normal skin. Immunoreactive MGSA/GRO alpha 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.