RNA-sequencing analysis of lung primary fibroblast response to eosinophil-degranulation products predicts downstream effects on inflammation, tissue remodeling and lipid metabolism.
RNA-sequencing analysis of lung primary fibroblast response to eosinophil-degranulation products predicts downstream effects on inflammation, tissue remodeling and lipid metabolism.
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DOI：
10.1186/s12931-017-0669-8
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发表时间：
2017-11-10
影响因子：
5.8
通讯作者：
Sandbo N
中科院分区：
文献类型：
--
作者：
Esnault S;Bernau K;Torr EE;Bochkov YA;Jarjour NN;Sandbo N
嗜酸性粒细胞与炎症和组织重塑的关联至少部分是由于它们释放毒性颗粒蛋白和其他介质，包括细胞因子。结缔组织成纤维细胞的活性影响组织重塑和随之而来的功能缺陷。过度的成纤维细胞活化、积聚和表型改变可导致纤维化和组织功能丧失。到目前为止，关于嗜酸性粒细胞如何通过激活成纤维细胞影响炎症和组织重塑的信息报道很少。我们最近已经表明，嗜酸性粒细胞激活IL-3导致一个强大的嗜酸性粒细胞脱粒免疫球蛋白G（IgG）包被板。因此，在本研究中，我们使用全转录组测序分析IL-3激活的嗜酸性粒细胞脱粒产物对原代人肺成纤维细胞（HLF）的影响。从用IL-3或IL-5预活化并随后在IgG上培养6小时以诱导脱粒的嗜酸性粒细胞获得条件培养基。将该条件培养基添加到人肺成纤维细胞（HLF）上24小时，然后对细胞裂解物进行全转录组测序以鉴定基因表达的总体变化。差异表达的基因使用免疫途径分析（IPA）进行分析，并通过qPCR进行验证。在HLF中，与对照成纤维细胞培养物相比，IL-3激活的嗜酸性粒细胞的条件培养基改变了300个基因的表达水平。在这300个基因中，35个编码已知蛋白质的基因的表达水平被IL-3与IL-5预活化的嗜酸性粒细胞上调。在35个上调的基因中，IPA鉴定出C3、CH 25 H、CXCL 1、CXCL 8、CYP 1A 1、ICAM 1、IL 6和UCN 2在炎症、组织重塑和脂质合成中具有下游功能。该分析结合先前嗜酸性粒细胞的RNA测序分析表明IL-1 β、OSM和TNFSF 12是成纤维细胞的潜在上游调节因子。这项研究已经确定了几种新的促炎和促重塑介质产生的成纤维细胞在活化的嗜酸性粒细胞。这些发现可能对嗜酸性粒细胞/成纤维细胞相互作用在嗜酸性粒细胞性疾病中的作用具有重要意义。本文的在线版本（10.1186/s12931-017-0669-8）包含补充材料，可供授权用户使用。
The association of eosinophils with inflammation and tissue remodeling is at least partially due to their release of toxic granule proteins and other mediators, including cytokines. Tissue remodeling and consequent functional defects are affected by activity of connective tissue fibroblasts. Exaggerated fibroblast activation, accumulation and change of phenotype may lead to fibrosis and loss of tissue function. So far, little information has been reported on how eosinophils affect inflammation and tissue remodeling via the activation of fibroblasts. We have recently shown that eosinophil activation with IL-3 led to a robust eosinophil degranulation on immunoglobin-G (IgG) coated plates. Thus, in the present study, we analyze the effects of IL-3-activated eosinophil degranulation products on primary human lung fibroblasts (HLF) using whole transcriptome sequencing. Conditioned media was obtained from eosinophils that were pre-activated with IL-3 or IL-5 and subsequently cultured for 6 h on IgG to induce degranulation. This conditioned media was added on human lung fibroblasts (HLF) for 24 h and the cell lysates were then subjected to whole transcriptome sequencing to identify global changes in gene expression. Differentially expressed genes were analyzed using the Ingenuity Pathway Analysis (IPA), and validated by qPCR. In HLF, the expression level of 300 genes was changed by conditioned media from IL-3-activated eosinophils compared to control fibroblast cultures. Among these 300 genes, the expression level of 35 genes coding for known proteins was upregulated by IL-3- versus IL-5-pre-activated eosinophils. Of the 35 upregulated genes, IPA identified C3, CH25H, CXCL1, CXCL8, CYP1A1, ICAM1, IL6 and UCN2 as having downstream functions on inflammation, tissue remodeling and lipid synthesis. This analysis combined with previous RNA sequencing analyses of eosinophils suggest IL-1ß, OSM and TNFSF12 as potential upstream regulators of fibroblasts. This study has identified several novel pro-inflammatory and pro–remodeling mediators produced by fibroblasts in response to activated eosinophils. These findings may have significant implications on the role of eosinophil/fibroblast interactions in eosinophilic disorders. The online version of this article (10.1186/s12931-017-0669-8) contains supplementary material, which is available to authorized users.
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嗜酸性粒细胞介导的小肠稳态和IgA产生中的IL-1β。
影响因子：
8
作者：
通讯作者：
--
DOI：
10.4049/jimmunol.1500871
发表时间：
2015-09-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Esnault S;Kelly EA;Shen ZJ;Johansson MW;Malter JS;Jarjour NN
通讯作者：
Jarjour NN
影响因子：
3.3
作者：
Hahn, Andrew D.;Cadman, Robert V.;Fain, Sean B.
通讯作者：
Fain, Sean B.
影响因子：
4.1
作者：
HEINO, J;HEINONEN, T
通讯作者：
HEINONEN, T
影响因子：
6.1
作者：
Batra, V;Musani, AI;Peters, SP
通讯作者：
Peters, SP