ABSTRACT
BACKGROUND: The aim of this study was to evaluate the effect of ß-Dmannuronic acid (M2000) on related miRNAs to dendritic cells (DCs) differentiation. DC-based immunosuppressive drugs can suppress the progression of autoimmune diseases, however, their notable side effects in increasing the risk of infectious diseases and cancers should be considered. The ß-D-mannuronic acid, as a novel non-steroidal anti-inflammatory agent, has been tested in various experimental models. METHOD: The effect of M2000 on expression of miRNA-155 and miRNA-221 was examined. To investigate how M2000 affects differentiation of human dendritic DCs in a defined inflammatory environment, human peripheral blood mononuclear cells were isolated from healthy blood and the monocytes were purified using anti-CD14 microbeads. The so isolated monocytes were subsequently incubated in the presence of M2000 in two different doses (3 and 6 mMol/well) adding granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 for inducing monocytes to immature DC and lipopolysaccharide for running DC differentiation. The expression of miRNA-155 and miRNA-221 were examined with Real Time PCR. RESULTS: The results demonstrate that M2000 has no significant side effect on expression of miR-155 and miR-221 in both immature DC and mature DC process in vitro. CONCLUSION: Our findings show that ß-D-mannuronic acid is a safe agent which has no adverse effect on regulatory miRNA-155 and miRNA-221 in dendritic cells.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Dendritic Cells/drug effects , Hexuronic Acids/pharmacology , Immunosuppressive Agents/pharmacology , MicroRNAs/genetics , Cell Differentiation/drug effects , Cells, Cultured , Dendritic Cells/cytology , Dendritic Cells/physiology , HumansABSTRACT
Multiple sclerosis is a complex disease with many different immune cells involved in its pathogenesis. Newly identified T helper cell 22 (Th22) is a subset of CD4(+) T cells with specific properties apart from other known CD4(+) T cell subsets with distinguished function and gene expression. Th22 cells are characterized by production of a distinct profile of effector cytokines, including interleukin (IL)-22, IL-13, and tumor necrosis factor-α (TNF- α). The frequency of Th22 and related cytokine IL-22 are increased in various autoimmune diseases. Recently, several studies have reported the changes in frequency and function of Th22 in multiple sclerosis. This review discusses the role of Th22 and its cytokine IL-22 in the immunopathogenesis of multiple sclerosis disease.
