title: 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.affiliation: Immunology and Reproductive Biology Lab, Medical School & State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China.
authors.forename: Hongye
authors.initials: H
authors.lastname: Fan
authors.forename: Guangfeng
authors.initials: G
authors.lastname: Zhao
authors.forename: Liu
authors.initials: L
authors.lastname: Liu
authors.forename: Fei
authors.initials: F
authors.lastname: Liu
authors.forename: Wei
authors.initials: W
authors.lastname: Gong
authors.forename: Xianqin
authors.initials: X
authors.lastname: Liu
authors.forename: Liu
authors.initials: L
authors.lastname: Yang
authors.forename: Jianjun
authors.initials: J
authors.lastname: Wang
authors.forename: Yayi
authors.initials: Y
authors.lastname: Hou
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003092:Colitis / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D016264:Dextran Sulfate; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology* / Q000627:therapeutic use; D008163:Luminescent Measurements; D008214:Lymphocytes / Q000187:drug effects; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D019718:Receptors, CXCR4 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
chemical_list: C514936:CXCR4 protein, mouse; D053583:Interleukin-1beta; D019718:Receptors, CXCR4; D016264:Dextran Sulfate