IL1β Induces Mesenchymal Stem Cells Migration and Leucocyte Chemotaxis Through NF-κB

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-1 beta: a representative inflammatory mediator. Microarray analysis of MSC treated with IL-1 beta 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-1 beta mainly increaseds the production of chemokines such as CCL5, CCL20, CXCL1, CXCL3, CXCL5, CXCL6, CXCL10, CXCL11 and CX(3)CL1, interleukins IL-6, IL-8, IL23A, IL32, Toll-like receptors TLR2, TLR4, CLDN1, metalloproteins MMP1 and MMP3, growth factors CSF2 and TNF-alpha, together with adhesion molecules ICAM1 and ICAM4. Functional analysis of MSC proliferation, migration and adhesion to extracellular matrix components revealed that IL-1 beta 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-1 beta treatment enhanced the ability of MSC to recruit monocytes and granulocytes in vitro. Blockade of NF-kappa I-2 transcription factor activation with I kappa B kinase beta (IKK beta) shRNA impaired MSC migration, adhesion and leucocyte recruitment, induced by IL-1 beta demonstrating that NF-kappa B pathway is an important downstream regulator of these responses. These findings are relevant to understanding the biological responses of MSC to inflammatory environments.