Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Effect of IL-1M-NM-2 on mesenchymal stem cells

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-1M-NM-2 as a representative inflammatory mediator. Microarray analysis of MSC treated with IL-1M-NM-2 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-1M-NM-2 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-1M-NM-2 did not affect proliferation whereas constitute a throphic factor for MSC and increases adhesion mainly to collagen and laminin. Moreover, IL-1M-NM-2 treatment enhanced the ability of MSC to recruit monocytes and granulocytes cells in vitro. Blockade of NFkM-NM-2 transcription factor activation with IM-NM-:B 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. Comparison between two experimental conditions, one sample for each condition

ORGANISM(S): Homo sapiens

SUBMITTER: FRANCISCO GARCIA

PROVIDER: E-GEOD-33755 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

IL1β induces mesenchymal stem cells migration and leucocyte chemotaxis through NF-κB.

Carrero Rubén R Cerrada Inmaculada I Lledó Elisa E Dopazo Joaquín J García-García Francisco F Rubio Mari-Paz MP Trigueros César C Dorronsoro Akaitz A Ruiz-Sauri Amparo A Montero José Anastasio JA Sepúlveda Pilar P

Stem cell reviews and reports 20120901 3

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 ...[more]

PMID: 22467443

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Project description:Tyrosine kinase inhibitors (TKI) are highly effective in treatment of chronic myeloid leukemia (CML) but do not eliminate leukemia stem cells (LSC), which remain a potential source of relapse. TKI treatment effectively inhibits BCR-ABL kinase activity in CML LSC, suggesting that additional kinase-independent mechanisms contribute to LSC preservation. We investigated whether signals from the bone marrow (BM) microenvironment protect CML LSC from TKI treatment. Coculture with human BM mesenchymal stromal cells (MSC) significantly inhibited apoptosis and preserved CML stem/progenitor cells following TKI exposure, maintaining colony forming ability and engraftment potential in immunodeficient mice. We found that the N-Cadherin receptor plays an important role in MSC-mediated protection of CML progenitors from TKI. N-Cadherin-mediated adhesion to MSC was associated with increased cytoplasmic N-Cadherin-M-NM-2-catenin complex formation, as well as enhanced M-NM-2-catenin nuclear translocation and transcriptional activity. Increased exogenous Wnt-mediated M-NM-2-catenin signaling played an important role in MSC-mediated protection of CML progenitors from TKI treatment. Our results reveal a close interplay between N-Cadherin and the Wnt-M-NM-2-catenin pathway in protecting CML LSC during TKI treatment. Importantly, these results reveal novel mechanisms of resistance of CML LSC to TKI treatment, and suggest new targets for treatment designed to eradicate residual LSC in CML patients. RNA was obtained from CML CD34+ cells treated with or without IM (5M-NM-<M) and MSC for 96 hours, amplified, labeled and hybridized to GeneChip 1.0 arrays (Affymetrix, Santa Clara, CA). Microarray data analysis was performed using R (version 2.9) with genomic analysis packages from Bioconductor (version 2.4). The 33297 probes represented on the microarray were filtered by cross-sample mean, and for standard deviation of greater than the 25% quantile, yielding 18624 probes representing 12553 genes. Linear regression was used to model the gene expression with the consideration of a 2x2 factorial design and matched samples. Differentially expressed genes were identified by calculating empirical Bayes moderated t-statistic, and p-values were adjusted by FDR using the M-bM-^@M-^\LIMMAM-bM-^@M-^] package. Gene Set Enrichment Analysis (GSEA) was performed using GSEA software version 2.04 to detect enrichment of predetermined gene sets using t-scores from all genes for 1263 gene sets in the C2 (curated gene sets) category from the Molecular Signature Database (MsigDB).

Dataset Information

Effect of IL-1M-NM-2 on mesenchymal stem cells

Publications

IL1β induces mesenchymal stem cells migration and leucocyte chemotaxis through NF-κB.

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