Interleukin-6 and Tumour Necrosis Factor-α differentially regulate lincRNA transcripts in cells of the innate immune system in vivo in human subjects with rheumatoid arthritis
Interleukin-6 and Tumour Necrosis Factor-α differentially regulate lincRNA transcripts in cells of the innate immune system in vivo in human subjects with rheumatoid arthritis
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DOI：
10.1016/j.cyto.2014.03.004
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发表时间：
2014-07-01
期刊：
影响因子：
3.8
通讯作者：
Laudes, Matthias
中科院分区：
文献类型：
--
作者：
Mueller, Nike;Doering, Frank;Laudes, Matthias
lincRNA最近被发现是非编码DNA序列的进化上保守的转录物，并且与细胞分化的调节有关。在人类中，分子研究表明lincRNA在癌症发展中的功能作用。本研究的目的是检查这些新的分子是否在体内由人类先天免疫系统细胞中的不同细胞因子特异性调节，以及lincRNA是否因此可能参与类风湿性关节炎（RA）的病理生理学。因此，在抗IL-6 R（托珠单抗）或抗TNF-α（阿达木单抗）治疗之前和之后从RA患者分离CD 14（+）单核细胞，并通过基于微阵列的实验分析lincRNA转录。正如预期的那样，我们发现lincRNA存在于RA患者的CD 14（+）单核细胞中。然而，在本研究中检查的7.419个lincRNA的总数中，只有非常小的数量被IL-6或TNF-α显著调节（85个lincRNA，对应于1.1%）。与IL-6相比，由于TNF-α调节的lincRNA的数量更高。有趣的是，所鉴定的lincRNA均不受IL-6和TNF-α两者的影响，表明lincRNA转录的调节对不同的细胞因子具有高度特异性。综上所述，我们的结果表明：（1）lincRNA是体内人类先天免疫系统细胞中特异性细胞因子的新型细胞内分子效应物;（2）lincRNA可能参与RA的分子病理生理学。(C)2014爱思唯尔有限公司版权所有。
lincRNAs recently have been discovered as evolutionary conserved transcripts of non-coding DNA sequences and have been implicated in the regulation of cellular differentiation. In humans, molecular studies have suggested a functional role for lincRNAs in cancer development. The aim of the present study was to examine whether these novel molecules are specifically regulated by different cytokines in cells of the innate immune system in humans in vivo and whether lincRNAs thereby might be involved in the pathophysiology of rheumatoid arthritis (RA). Therefore, CD 14(+) monocytes were isolated from RA patients before and after anti-IL-6R (tocilizumab) or anti-TNF-alpha (adalimumab) therapy and lincRNA transcription was analysed by a microarray based experiment. As expected, we found lincRNAs to be present in CD14(+) monocytes of RA patients. However, of the total number of 7.419 lincRNAs examined in this study only a very small number was significantly regulated by either IL-6 or TNF-alpha (85 lincRNAs, corresponding to 1.1%). The numbers of lincRNAs regulated was higher due to TNF-alpha compared to IL-6. Interestingly, none of the identified lincRNAs was influenced by both, IL-6 and TNF-alpha, suggesting the regulation of lincRNA transcription to be highly specific for distinct cytokines. Taken together, our results suggest (1) that lincRNAs are novel intracellular molecular effectors of specific cytokines in cells of the innate immune system in humans in vivo and (2) that lincRNAs might be involved in the molecular pathophysiology of RA. (C) 2014 Elsevier Ltd. All rights reserved.