Gene expression clusters of a lipopolysaccharide-stimulated pathway in peripheral blood monocytes of Japanese patients with Crohn's disease

Y. NAITO, T. TAKAGI, K. MIZUSHIMA, M. UETA, S. KINOSHITA, O. HANDA, S. KOKURA, H. ICHIKAWA, N. YOSHIDA, T. YOSHIKAWA
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Abstract

Summary

Background

Recent reports support the notion that patients with Crohn's disease have a dysregulated innate immune response to endogenous flora.

Aim

To reveal the distinct gene expression clusters of a lipopolysaccharide-stimulated pathway in the peripheral blood monocytes of Japanese patients with Crohn's disease.

Materials and methods

Total RNA was extracted from peripheral blood monocytes of four patients in the remission stage of Crohn's disease as well as four controls, and gene expression profiles before and after lipopolysaccharide stimulation were investigated using a high-density oligonucleotide probe array. To focus on innate immunity, the expression of genes to be studied was narrowed down to 118 probe sets which were selected using the following keywords: lipopolysaccharide, toll, myd and tir along with a software of NetAffx Analysis Center.

Results

Using hierarchical clustering analysis, we picked up to 44 and 36 probe sets for which expression had decreased before and after lipopolysaccharide stimulation, respectively, in patients with Crohn's disease compared with healthy volunteers. The expression of TLR5, 7, MyD88, SIGIRR, and Tollip was decreased both before and after lipopolysaccharide stimulation in patients with Crohn's disease.

Conclusion

We found several interesting clusters in monocytes before and after stimulation with lipopolysaccharide. These genes may have been responsible for the immunological differences between the Crohn's disease and control patients.

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日本克罗恩病患者外周血单核细胞中脂多糖刺激通路的基因表达簇
背景最近的报道支持了克罗恩病患者对内源性菌群的先天免疫反应失调的观点。目的揭示日本克罗恩病患者外周血单核细胞中脂多糖刺激通路的不同基因表达簇。材料与方法从4例克罗恩病缓解期患者和4例对照组外周血单核细胞中提取总RNA,采用高密度寡核苷酸探针阵列检测脂多糖刺激前后的基因表达谱。为了关注先天免疫,我们利用NetAffx分析中心的软件,以脂多糖(lipopolaccharide)、toll、myd和tir为关键词,将待研究基因的表达范围缩小到118个探针组。结果通过分层聚类分析,与健康志愿者相比,克罗恩病患者在脂多糖刺激前后分别有44个和36个探针组表达下降。克罗恩病患者在脂多糖刺激前后,TLR5、7、MyD88、SIGIRR、Tollip的表达均降低。结论脂多糖刺激前后单核细胞内出现了一些有趣的聚集。这些基因可能是导致克罗恩病患者和对照组患者免疫差异的原因。
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