Interleukin 1 receptor antagonist mediates the antiinflammatory and antifibrotic effect of mesenchymal stem cells during lung injury

Abstract

bleomycin ͉ inflammation

Multipotent mesenchymal stromal cells for autoimmune diseases: teaching new dogs old tricks

“…55 This effect was achieved through the reduction of inflammation mediated by IL-1R antagonist secreted by MSCs and capable of antagonizing IL-1a secreting T-cells and TNF-a producing macrophages. 43 Similar results were obtained by the infusion of MSCs in a murine model with acute lung injury leading to a decreased production of pro-inflammatory cytokines and increased levels of IL-10 56 and in a murine hepatic fibrosis model (carbon tetrachloride induced) using an MSC line bearing the fetal liver kinase-1 (FLK1) marker. 57 In all these studies, the protective effect of MSCs on lung cells occurred despite limited levels of engraftment in the target organ and transdifferentiation.…”

“…However, transwell experiments have shown putative paracrine soluble factors (Table 1) including hepatocyte growth factor (HGF) and transforming growth factor-b1 (TGF-b1), 22 prostaglandin E 2 39,30 indoleamine 2,3-deoxygenase, 40 inducible NO synthetase resulting in Stat 5 inhibition in lymphocytes, 41 soluble HLA-G 42 and soluble IL-1 receptor. 43 Current data, however, show that these molecules play only a limited role and others are yet to be discovered.…”

Mesenchymal stem cells: mechanisms of potential therapeutic benefit in ARDS and sepsis

“…33 TSG-6, a potent anti-infl ammatory protein, has also been identifi ed as a potential paracrine factor. In a murine model of lung injury using LPS, MSCs upregulated expression of TSG-6, while decreasing cytokine levels and infl ammatory cell counts in BAL fl uid.…”

Implications of the immunoregulatory functions of mesenchymal stem cells in the treatment of human liver diseases

“…In models of lung or other organ injury, MSC therapy can downregulate local and systemic proinflammatory responses by secreting IL-1 receptor antagonists, and it can upregulate anti-inflammatory cytokines such as IL-10. 10 Furthermore, because of the lack of human leukocyte antigen (HLA) class II and costimulatory molecules such as CD80, CD86, CD40 or CD40L, MSC transplantation does not result in hostversus-graft responses. 11 MSCs can also produce some anti-apoptotic cytokines such as stromal cell-derived factor-1 and vascular endothelial growth factor, which efficiently reduce the apoptosis of recipient cells via the stromal cell-derived factor-1/CX chemokine receptor-4 axis.…”