Dataset Information

IL1? induces mesenchymal stem cells migration and leucocyte chemotaxis through NF-?B.

ABSTRACT: 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?: a representative inflammatory mediator. Microarray analysis of MSC treated with IL-1? 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? 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-?, together with adhesion molecules ICAM1 and ICAM4. Functional analysis of MSC proliferation, migration and adhesion to extracellular matrix components revealed that IL-1? 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? treatment enhanced the ability of MSC to recruit monocytes and granulocytes in vitro. Blockade of NF-?? transcription factor activation with I?B kinase beta (IKK?) shRNA impaired MSC migration, adhesion and leucocyte recruitment, induced by IL-1? demonstrating that NF-?B pathway is an important downstream regulator of these responses. These findings are relevant to understanding the biological responses of MSC to inflammatory environments.

SUBMITTER: Carrero R

PROVIDER: S-EPMC3412085 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

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

Similar Datasets

Project description:BACKGROUND:Mesenchymal stem cells (MSCs) are known to home to injured and inflamed regions via the bloodstream to assist in tissue regeneration in response to signals of cellular damage. However, the factors and mechanisms that affect their transendothelial migration are still unclear. In this study, the mechanisms involved in interleukin-1? (IL-1?) enhancing the transendothelial migration of MSCs were investigated. METHODS:Immunofluorescence staining and Western blotting were used to observe IL-1?-induced CXC chemokine receptor 3 (CXCR3) expression on MSCs. Quantitative real-time PCR and ELISA were used to demonstrate IL-1? upregulated both chemokine (C-X-C motif) ligand 9 (CXCL9) mRNA and CXCL9 ligand secretion in human umbilical vein endothelial cells (HUVECs). Monolayer co-cultivation, agarose drop chemotaxis, and transwell assay were conducted to investigate the chemotaxis invasion and transendothelial migration ability of IL-1?-induced MSCs in response to CXCL9. RESULTS:In this study, our immunofluorescence staining showed that IL-1? induces CXCR3 expression on MSCs. This result was confirmed by Western blotting. Following pretreatment with protein synthesis inhibitor cycloheximide, we found that IL-1? induced CXCR3 on the surface of MSCs via protein synthesis pathway. Quantitative real-time PCR and ELISA validated that IL-1? upregulated both CXCL9 mRNA and CXCL9 ligand secretion in HUVECs. In response to CXCL9, chemotaxis invasion and transendothelial migration ability were increased in IL-1?-stimulated MSCs. In addition, we pretreated MSCs with CXCR3 antagonist AMG-487 and p38 MAPK inhibitor SB203580 to confirm CXCR3-CXCL9 interaction and the role of CXCR3 in IL-1?-induced chemotaxis invasion and transendothelial migration. CONCLUSION:We found that IL-1? induces the expression of CXCR3 through p38 MAPK signaling and that IL-1? also enhances CXCL9 ligand secretion in HUVECs. These results indicated that IL-1? promotes the transendothelial migration of MSCs through CXCR3-CXCL9 axis. The implication of the finding could enhance the efficacy of MSCs homing to target sites.

Dataset Information

IL1? induces mesenchymal stem cells migration and leucocyte chemotaxis through NF-?B.

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets