Pre-treatment with IL-1β enhances the efficacy of MSC transplantation in DSS-induced colitis.

Abstract

Mesenchymal stem cells (MSCs) have been used experimentally for treating inflammatory disorders, partly due to their immunosuppressive properties. Although interleukin-1β (IL-1β) is one of the most important inflammatory mediators, growing evidence indicates that IL-1β signaling elicits the immunosuppressive properties of MSCs. However, it remains unclear how IL-1β signaling accomplishes this activity. Here, we focus on the therapeutic efficacy of IL-1β-primed MSCs in the dextran sulfate sodium (DSS)-induced colitis model, in addition to the underlining mechanisms. We first found that IL-1β-primed MSCs, without any observable phenotype change in vitro, significantly attenuated the development of DSS-induced murine colitis. Moreover, IL-1β-primed MSCs modulated the balance of immune cells in the spleen and the mesenteric lymph nodes (MLNs) through elevating cyclooxygenase-2 (COX-2), IL-6 and IL-8 expression and influencing the polarization of peritoneal macrophages. Importantly, IL-1β-primed MSCs possessed an enhanced ability to migrate to the inflammatory site of the gut via upregulation of chemokine receptor type 4 (CXCR4) expression. In summary, IL-1β-primed MSCs have improved efficacy in treating DSS-induced colitis, which at least partly depends on their increased immunosuppressive capacities and enhanced migration ability.

• Authors: Hongye Fan, Guangfeng Zhao, Liu Liu, Fei Liu, Wei Gong, Xianqin Liu, Liu Yang, Jianjun Wang, Yayi Hou
• Journal: Cellular & molecular immunology (Cell Mol Immunol) Vol. 9 Issue 6 Pg. 473-81 (Nov 2012) ISSN: 2042-0226 [Electronic] China
• PMID: 23085948 (Publication Type: Journal Article)

Chemical References

• CXCR4 protein, mouse
• Interleukin-1beta
• Receptors, CXCR4
• Dextran Sulfate

Topics

• Animals
• Cell Movement (drug effects)
• Cell Shape (drug effects)
• Cell Survival (drug effects)
• Colitis (drug therapy, immunology, pathology, therapy)
• Dextran Sulfate
• Humans
• Interleukin-1beta (pharmacology, therapeutic use)
• Luminescent Measurements
• Lymphocytes (drug effects)
• Mesenchymal Stem Cell Transplantation
• Mesenchymal Stem Cells (cytology, drug effects, metabolism)
• Mice
• Mice, Inbred C57BL
• Phenotype
• Receptors, CXCR4 (metabolism)
• Signal Transduction (drug effects)
• Up-Regulation (drug effects)