Autschbach Frank, Giese Thomas, Gassler Nikolaus, Sido Bernd, Heuschen Gundi, Heuschen Udo, Zuna Ivan, Schulz Patricia, Weckauf Helgard, Berger Irina, Otto Herwart F, Meuer Stefan C
Institute of Pathology, Heidelberg University, Im Neuenheimer Feld 220/221, 69120 Heidelberg, Germany.
Virchows Arch. 2002 Nov;441(5):500-13. doi: 10.1007/s00428-002-0684-z. Epub 2002 Jul 23.
To define mediator profiles in inflamed and noninflamed areas in inflammatory bowel disease (IBD) we analyzed the expression of 35 messenger-RNAs (mRNAs) encoding cytokines, chemokines, and some related molecules in transmural gut tissues (n=138) from patients with ulcerative colitis (UC), Crohn's disease (CD), and inflammatory and normal controls by real-time quantitative reverse transcription polymerase chain reaction. Using sample collectives with a comparable degree of inflammation, most parameters investigated showed similarly increased mRNA expression levels in both active UC and CD. This included proinflammatory cytokines, but also interferon (IFN) gamma and several IFN-gamma inducible chemokines. Only macrophage inflammatory protein (MIP)-2alpha mRNA was expressed at higher levels in inflamed UC vs. CD. IH revealed that MIP-2alpha protein was produced mainly by intestinal epithelial cells. Importantly, in histologically noninflamed/inactive IBD samples mRNAs for several mediators were significantly enhanced, accompanied by elevated levels of migration-inhibition factor related protein (MRP) 14 transcripts. CD14 positive macrophages were found especially in noninflamed/inactive UC, many of which coexpressed the RFD-7 antigen. Our results indicate a substantial overlap in cytokine/chemokine mRNA expression in UC and CD. Elevated mediator expression is evident in noninflamed/inactive areas in both diseases. Local recruitment of MRP-14 positive leukocytes might contribute to this phenomenon. In inactive UC a phenotypically altered population of macrophages expressing CD14 might play an additional role.
为了确定炎症性肠病（IBD）中炎症和非炎症区域的介质谱，我们通过实时定量逆转录聚合酶链反应分析了来自溃疡性结肠炎（UC）、克罗恩病（CD）患者以及炎症和正常对照的透壁肠组织（n = 138）中35种编码细胞因子、趋化因子及一些相关分子的信使核糖核酸（mRNA）的表达。在具有相似炎症程度的样本集中，大多数研究参数显示，在活动期UC和CD中，mRNA表达水平均有类似程度的升高。这包括促炎细胞因子，还有干扰素（IFN）γ以及几种IFN-γ诱导的趋化因子。仅巨噬细胞炎性蛋白（MIP）-2α mRNA在炎症期UC中的表达水平高于CD。免疫组化显示，MIP-2α蛋白主要由肠上皮细胞产生。重要的是，在组织学上非炎症/非活动期IBD样本中，几种介质的mRNA显著增强，同时迁移抑制因子相关蛋白（MRP）14转录本水平升高。CD14阳性巨噬细胞尤其在非炎症/非活动期UC中被发现，其中许多共表达RFD-7抗原。我们的结果表明，UC和CD中细胞因子/趋化因子mRNA表达存在大量重叠。在两种疾病的非炎症/非活动区域，介质表达均明显升高。MRP-14阳性白细胞的局部募集可能导致了这一现象。在非活动期UC中，表达CD14的表型改变的巨噬细胞群体可能起了额外作用。
