Interleukin-1 receptor antagonist (IL-1Ra) and IL-1Ra producing mesenchymal stem cells as modulators of diabetogenesis.
The increase of pro-inflammatory cytokines and oxidative stress leads to beta-cell damage and promotes beta-cells apoptosis, in types I and II of diabetes mellitus. Therefore, blocking of pro-inflammatory cytokines should be an effective way for the treatment of diabetes mellitus. When IL-1 occupies its receptor, various pro-inflammatory events are initiated including the synthesis and releases of chemokines and these chemokines attract neutrophils, macrophages, and lymphocytes that cause tissue inflammation. IL-1Ra is a naturally occurring cytokine and is the inhibitor of IL-1. When IL-1Ra binds to the IL-1 receptor, binding of IL-1 is blocked by IL-1Ra and pro-inflammatory signal from IL-1 receptor is stopped. There are mounting evidences to suggest that anti-inflammatory IL-1Ra reduces the inflammatory effects of IL-1 and preserves cell function in both types of diabetes. Therefore, IL-1Ra maybe a new therapeutic agent for diabetes mellitus types I and II. Mesenchymal stem cells (MSCs) are self-renewable multipotent stromal cells that have immunomodulatory capacity. Recently, well characterized subpopulations of MSCs which express IL-1Ra have been described. IL-1Ra expressed by these MSCs effectively binds to IL-1 receptor and protects tissues from inflammation-induced injuries. It has been previously shown that bone marrow-derived MSC therapy could be considered for the treatment of diabetes mellitus type 1 and complications of diabetes mellitus. This review presents understanding of potential use of IL-1Ra and MSCs as modulators of diabetogenesis.
Faculty of Medicine, Center for Molecular Medicine, University of Kragujevac, Kragujevac, Serbia.
Vladislav
V
Volarevic
Ahmed
A
Al-Qahtani
Nebojsa
N
Arsenijevic
Sladjana
S
Pajovic
Miodrag L
ML
Lukic
D000818:Animals; D002986:Clinical Trials as Topic; D003922:Diabetes Mellitus, Type 1 / Q000517:prevention & control / Q000628:therapy*; D003924:Diabetes Mellitus, Type 2 / Q000517:prevention & control / Q000628:therapy*; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000378:metabolism / Q000627:therapeutic use*; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D017472:Receptors, Interleukin-1 / Q000378:metabolism; D016896:Treatment Outcome
D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D017472:Receptors, Interleukin-1