IL1β induces mesenchymal stem cells migration and leucocyte chemotaxis through NF-κB.
IL1β induces mesenchymal stem cells migration and leucocyte chemotaxis through NF-κB.
复制标题
DOI：
10.1007/s12015-012-9364-9
复制
发表时间：
2012-09
影响因子：
4.8
通讯作者：
Sepulveda, Pilar
中科院分区：
文献类型：
--
作者：
Carrero, Ruben;Cerrada, Inmaculada;Lledo, Elisa;Dopazo, Joaquin;Garcia-Garcia, Francisco;Rubio, Mari-Paz;Trigueros, Cesar;Dorronsoro, Akaitz;Ruiz-Sauri, Amparo;Anastasio Montero, Jose;Sepulveda, Pilar
间充质干细胞通常被移植到炎症环境中，在那里它们能够存活并通过知之甚少的机制调节宿主免疫反应。本文分析了MSC对IL-1β的反应性。用IL-1β处理MSC的微阵列分析显示，这种细胞因子激活了一组与生物学过程相关的基因，如细胞存活、细胞迁移、细胞粘附、趋化因子产生、诱导血管生成和调节免疫应答。通过实时PCR和功能测定的进一步更详细的分析显示，IL-1β主要增加趋化因子如CCL 5、CCL 20、CXCL 1、CXCL 3、CXCL 5、CXCL 6、CXCL 10、CXCL 11和CX 3CL 1，白细胞介素IL-6、IL-8、IL 23 A、IL 32，Toll样受体TLR 2、TLR 4、CLDN 1，金属蛋白MMP 1和MMP 3，生长因子CSF 2和TNF-α，以及粘附分子ICAM 1和ICAM 4。MSC增殖、迁移和与细胞外基质成分粘附的功能分析显示，IL-1β不影响增殖，但也用于诱导营养因子的分泌和与ECM成分如胶原和层粘连蛋白的粘附。IL-1β处理增强MSC在体外募集单核细胞和粒细胞的能力。用IκB激酶β（IKKβ）shRNA阻断NF-κβ转录因子的激活，可损害IL-1β诱导的MSC迁移、粘附和白细胞募集，表明NF-κB通路是这些反应的重要下游调节因子。这些发现与理解MSC对炎症环境的生物学反应有关。本文的在线版本（doi：10.1007/s12015-012-9364-9）包含补充材料，可供授权用户使用。
Mesenchymal stem cells are often transplanted into inflammatory environments where they are able to survive and modulate host immune responses through a poorly understood mechanism. In this paper we analyzed the responses of MSC to IL-1β: a representative inflammatory mediator. Microarray analysis of MSC treated with IL-1β revealed that this cytokine activateds a set of genes related to biological processes such as cell survival, cell migration, cell adhesion, chemokine production, induction of angiogenesis and modulation of the immune response. Further more detailed analysis by real-time PCR and functional assays revealed that IL-1β mainly increaseds the production of chemokines such as CCL5, CCL20, CXCL1, CXCL3, CXCL5, CXCL6, CXCL10, CXCL11 and CX3CL1, interleukins IL-6, IL-8, IL23A, IL32, Toll-like receptors TLR2, TLR4, CLDN1, metalloproteins MMP1 and MMP3, growth factors CSF2 and TNF-α, together with adhesion molecules ICAM1 and ICAM4. Functional analysis of MSC proliferation, migration and adhesion to extracellular matrix components revealed that IL-1β did not affect proliferation but also served to induce the secretion of trophic factors and adhesion to ECM components such as collagen and laminin. IL-1β treatment enhanced the ability of MSC to recruit monocytes and granulocytes in vitro. Blockade of NF-κβ transcription factor activation with IκB kinase beta (IKKβ) shRNA impaired MSC migration, adhesion and leucocyte recruitment, induced by IL-1β demonstrating that NF-κB pathway is an important downstream regulator of these responses. These findings are relevant to understanding the biological responses of MSC to inflammatory environments. The online version of this article (doi:10.1007/s12015-012-9364-9) contains supplementary material, which is available to authorized users.
登录
查看更多内容
影响因子：
14.9
作者：
Al-Shahrour F;Minguez P;Tárraga J;Medina I;Alloza E;Montaner D;Dopazo J
通讯作者：
Dopazo J
影响因子：
29
作者：
Baker RG;Hayden MS;Ghosh S
通讯作者：
Ghosh S
影响因子：
3.2
作者：
Bujak, Marcin;Frangogiannis, Nikolaos G.
通讯作者：
Frangogiannis, Nikolaos G.
影响因子：
37.8
作者：
Davani, S;Marandin, A;Kantelip, JP
通讯作者：
Kantelip, JP
影响因子：
20.3
作者：
Kawada, H;Fujita, J;Fukuda, K
通讯作者：
Fukuda, K