IL1β Induces Mesenchymal Stem Cells Migration and Leucocyte Chemotaxis Through NF-κB
| Autor: | Inmaculada Cerrada, Joaquín Dopazo, Akaitz Dorronsoro, Amparo Ruiz-Sauri, Francisco García-García, José Anastasio Montero, César Trigueros, Elisa Lledó, Pilar Sepúlveda, Mari-Paz Rubio, Rubén Carrero |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Cancer Research
Chemokine Migration and adhesion medicine.medical_treatment Interleukin-1beta Biology Article Interleukin 1β Extracellular matrix Cell Movement Cell Adhesion Leukocytes medicine Humans Cell adhesion Cell Proliferation Oligonucleotide Array Sequence Analysis Cell adhesion molecule Gene Expression Profiling Chemotaxis NF-kappa B Mesenchymal Stem Cells Cell migration Cell Biology Fibronectins I-kappa B Kinase Cell biology Chemotaxis Leukocyte HEK293 Cells CXCL3 Cytokine Gene Knockdown Techniques biology.protein Intercellular Signaling Peptides and Proteins RNA Interference Collagen Laminin Chemokines Inflammation Mediators Stem cell Signal Transduction Developmental Biology |
| Zdroj: | Stem Cell Reviews |
| ISSN: | 1558-6804 1550-8943 |
| DOI: | 10.1007/s12015-012-9364-9 |
| Popis: | 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. Electronic supplementary material The online version of this article (doi:10.1007/s12015-012-9364-9) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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