From the Molecular Immunology Unit, Hospital Universitario Puerta de Hierro Majadahonda, 28222 Majadahonda, Madrid, Spain.
J Biol Chem. 2014 Jan 24;289(4):2457-68. doi: 10.1074/jbc.M113.521161. Epub 2013 Dec 4.
Pericytes and mesenchymal stem cells (MSCs) are ontogenically related, and in fact, no significant phenotypic differences could be observed by flow cytometry. Transcriptome analysis of human pericytes and MSCs revealed that 43 genes were up-regulated more than 10-fold in pericytes compared with MSCs. Identification of Toll-like receptor 4 (TLR4) as one of the most abundant RNA species in pericytes with respect to MSCs and confirmation of TLR4 expression on the cell surface led us to obtain a comprehensive overview of the expression program of lipopolysaccharide (LPS)-stimulated pericytes. Transcriptional profiling of LPS-treated cells revealed that 22 genes were up-regulated more than 5-fold. Of them, 10 genes encoded chemokines and cytokines (CXCL10, CCL20, IL8, CXCL1, IL6, CCL2, IL1B, CXCL2, IL1A, and CXCL6), and three genes encoded adhesion molecules (ICAM1, VCAM1, and SELE). LPS induced nuclear translocation of the transcription factor NF-κB in stimulated pericytes. Moreover, inhibition of NF-κB activation by SC-514 blocked LPS-induced up-regulation of a subset of chemokine genes, confirming the key role of NF-κB in LPS signaling in pericytes. At the protein level, we assessed the secretion of the proinflammatory cytokines and chemokines IL-6, IL-8, CXCL1, CXCL2, CXCL3, and CCL2 not only after LPS treatment but also in HMGB1-stimulated pericytes. Up-regulation of the adhesion molecules ICAM-1 and VCAM-1 resulted in an increased adhesion of peripheral blood leukocytes to an LPS-treated pericyte monolayer. The role of pericytes in the inflammatory context has been scarcely addressed; according to these results, pericytes should be considered as active players in the inflammatory cascade with potential physiopathological implications.
周细胞和间充质干细胞（MSCs）在胚胎发生上是相关的，事实上，通过流式细胞术观察不到它们之间存在明显的表型差异。对人周细胞和 MSCs 的转录组分析表明，与 MSCs 相比，43 个基因在周细胞中上调超过 10 倍。鉴定 Toll 样受体 4（TLR4）为周细胞中相对于 MSCs 最丰富的 RNA 之一，并证实 TLR4 在细胞表面的表达，使我们能够全面了解 LPS 刺激的周细胞的表达程序。对 LPS 处理的细胞进行转录谱分析显示，有 22 个基因上调超过 5 倍。其中，10 个基因编码趋化因子和细胞因子（CXCL10、CCL20、IL8、CXCL1、IL6、CCL2、IL1B、CXCL2、IL1A 和 CXCL6），3 个基因编码粘附分子（ICAM1、VCAM1 和 SELE）。LPS 诱导刺激的周细胞中转录因子 NF-κB 的核转位。此外，通过 SC-514 抑制 NF-κB 激活阻断了 LPS 诱导的一组趋化因子基因的上调，证实了 NF-κB 在 LPS 信号通路中在周细胞中的关键作用。在蛋白质水平上，我们不仅评估了 LPS 处理后，还评估了 HMGB1 刺激的周细胞中促炎细胞因子和趋化因子 IL-6、IL-8、CXCL1、CXCL2、CXCL3 和 CCL2 的分泌。粘附分子 ICAM-1 和 VCAM-1 的上调导致外周血白细胞对 LPS 处理的周细胞单层的粘附增加。周细胞在炎症环境中的作用很少被涉及；根据这些结果，周细胞应该被视为炎症级联中的活跃参与者，具有潜在的生理病理学意义。
