ABSTRACT: Mesenchymal stem cells are often transplanted in inflammatory environments and they are able to survive and modulate host immune responses through mechanism poorly understood. In this paper we analyzed biological responses of MSC in response IL-1β as a representative inflammatory mediator. Microarray analysis of MSC treated with IL-1β revealed that this cytokine activates a set of biological process related with cell survival, cell migration, cell adhesion, chemokine production, induction of angiogenesis and modulation of immune response. Further analysis by real-time PCR and functional assays revealed that IL-1β mainly increases production of chemokines 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, 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 whereas constitute a throphic factor for MSC and increases adhesion mainly to collagen and laminin. Moreover, IL-1β treatment enhanced the ability of MSC to recruit monocytes and granulocytes cells in vitro. Blockade of NFkβ transcription factor activation with IκB kinase beta (IKKb) siRNA impaired MSC migration, adhesion and leucocyte recruitment, indicating that NF-kB signaling pathway is the main mechanism implicated in these biological processes. These findings are relevant for designing protocols that implicate MSC delivery into inflammatory environments.
