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-1b (IL-1b) is one of the most important inflammatory mediators, growing evidence indicates that IL-1b signaling elicits the immunosuppressive properties of MSCs. However, it remains unclear how IL-1b signaling accomplishes this activity. Here, we focus on the therapeutic efficacy of IL-1b-primed MSCs in the dextran sulfate sodium (DSS)-induced colitis model, in addition to the underlining mechanisms. We first found that IL-1b-primed MSCs, without any observable phenotype change in vitro, significantly attenuated the development of DSS-induced murine colitis. Moreover, IL-1b-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-1b-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-1b-primed MSCs have improved efficacy in treating DSS-induced colitis, which at least partly depends on their increased immunosuppressive capacities and enhanced migration ability.

Stromal cell-derived factor-1-directed bone marrow mesenchymal stem cell migration in response to inflammatory and/or hypoxic stimuli

“…18 Additionally, it was found that pretreatment with IL-1b and/or TNF-a can enhance cell migration by upregulating CXCR4 expression. 13,51 In addition to the growing evidence that stem cells can be isolated from clinically inflamed human tissue, there are also indications that these 'inflamed' cells have a stronger potential to migrate. 52,53 All of these findings suggest that inflammatory conditions can enhance stem cell migration potential.…”

“…12 In contrast, pretreatment with IL-1b enhanced the efficacy of MSC transplantation in treating dextran sulfate sodium (DSS)-induced colitis, which at least partially depended on an enhancement in cell migration ability. 13 Moreover, short-term stimulation of BMMSCs with a cocktail of cytokines resulted in upregulation of both cell surface and intracellular CXC chemokine receptor 4 (CXCR4). These changes increased the cells' in vitro migration capacity toward stromal cell-derived factor-1 (SDF-1) as well as their homing behavior to bone marrow following intravenous infusion into sublethally irradiated NOD/SCID mice.…”

The roles of immune cells in bone healing; what we know, do not know and future perspectives

“…Thus, NK cells and T-lymphocytes are linked to the licensing of MSCs as major sources of TNF-a that is highly expressed during both inflammatory and repair phases [45]. Together with IFN-g and TNF-a, MSCs that are activated by IL-1 can perform immunosuppressive functions associated with the production of prostaglandin 2 (PGE2) and IL-8 [46]. Furthermore, it has been shown that IL-17 is another licensing cytokine that can enhance the immunosuppressive functions of MSCs both in vivo and in vitro [47].…”

Suppressor Cells – The Basis of Immunopathogenesis Autoimmune Diseases

“…18, 1 2016, № 1 [20,22]. Сами МСК также обладают супрессор-ной активностью, но только после стимуляции их различными цитокинами [16]. Кстати, эта характеристика МСК является их принципиаль-ным отличием от другой популяции стволовых клеток, от ПСКК, описание супрессорной ак-тивности которых отсутствует в литературе.…”