Glucocorticoid receptor expression in inflammatory bowel disease:: evidence for a mucosal down-regulation in steroid-unresponsive ulcerative colitis
Glucocorticoid receptor expression in inflammatory bowel disease:: evidence for a mucosal down-regulation in steroid-unresponsive ulcerative colitis
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DOI：
10.1046/j.1365-2036.2003.01802.x
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发表时间：
2004-01-01
影响因子：
7.6
通讯作者：
Ramadori, G
中科院分区：
文献类型：
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作者：
Raddatz, D;Middel, P;Ramadori, G
背景：糖皮质激素(GC)在减轻炎症方面发挥着重要作用。糖皮质激素受体(GR)的表达是激素敏感性的重要决定因素。目的：探讨GR在炎症性肠病中的表达是否发生了改变，以及GR的表达是否与疾病的活动性有关，并可预测糖皮质激素的疗效。从24例溃疡性结肠炎、18例克罗恩病患者和11例正常对照的外周血中分离出单个核细胞。用定量逆转录聚合酶链式反应(RT-PCR)检测GR基因的表达，并与胃镜下表现、临床活动性及GC治疗结果相关。结果：在炎症性肠病患者中，GR的表达与对照组无差异。然而，在GC反应受损的溃疡性结肠炎患者的活检中，GR减少。抑制亚型GRβ的表达比GRα低100-1000倍。结论：炎症性肠病全身性和粘膜GR基因表达无明显改变。然而，在溃疡性结肠炎患者中，粘膜GR低表达可能预测GC治疗的结果。GRβ的低表达挑战了其在炎症性肠病激素抵抗中的作用。
Background: Glucocorticoids (GC) play a major role in the attenuation of inflammation. Glucocorticoid receptor (GR) expression is an important determinant of steroid sensitivity.Aims: To investigate whether GR mRNA expression is altered in inflammatory bowel disease, and whether GR mRNA expression correlates with disease activity and may predict response to GC therapy.Methods: Mucosal biopsies were taken from 33 patients with ulcerative colitis, 21 with Crohn's disease and 11 controls. Peripheral blood mononuclear cells were isolated from 24 ulcerative colitis and 18 Crohn's disease patients and 11 controls. GR mRNA was measured by quantitative reverse transcriptase polymerase chain reaction (RT-PCR), and correlated to endoscopic findings, clinical activity and outcome of GC therapy. In a subset of subjects GR localisation was shown by immunohistochemistry.Results: In patients with inflammatory bowel disease GR expression was not different from controls. However, GR was decreased in biopsies from ulcerative colitis patients with impaired GC response. The inhibitory subtype GRbeta was expressed 100-1000 times lower than GRalpha. GR immunoreactivity was identified in immune and epithelial cells except for colonic crypts.Conclusion: In inflammatory bowel disease systemic and mucosal GR mRNA expression is not altered. However, in ulcerative colitis patients, low mucosal GR expression may predict the outcome of GC therapy. The low expression of GRbeta challenges its role in steroid refractoriness in inflammatory bowel disease.