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Zi Ye, Chaokui Wang, Aize Kijlstra, Peizeng Yang; Regulatory Effect of Interleukin 37 in Behcet's disease. Invest. Ophthalmol. Vis. Sci. 2013;54(15):5371.
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Interleukin 37 has been found to have significant regulatory role in innate immune response. This study was to determine its role in the pathogenesis of Behcet’s disease (BD).
IL-37 mRNA expression in peripheral blood mononuclear cells (PBMCs) from BD patients and normal controls were measured by RT-PCR. PBMCs and monocyte-derived Dendritic Cells (DCs) were cultured with or without IL-37. The levels of cytokines in the supernatants of PBMCs and DCs were measured by ELISA. The IL-37R(IL-18Rα) expression, DCs surface markers, reactive oxygen species(ROS) production and mitogen-activated protein kinase (MAPK) activation were measured by flow cytometry. The effect of IL-37-treated DCs on the development of CD4+ T cells was measured by ELISA and flow cytometry.
IL-37 mRNA expression was significantly decreased in PBMCs from active BD patients compared with inactive BD patients and normal controls. PBMCs and DCs stimulated with rIL-37 showed a decreased expression of IL-6, IL-1β and TNF-α, and a higher production of IL-27. rIL-37 inhibited the production of ROS by DCs and reduced the activation of ERK1/2, JNK and P38 MAPK in DCs. rIL-37-treated DCs inhibited Th17 and Th1 cell response as compared with control DCs. However, rIL-37 did not have any influence on DCs surface markers (CD40, CD86, CD80 and HLA-DR) and IL-10 production by PBMCs or DCs.
This study showed that decreased IL-37 expression in active BD patients could trigger the production of pro-inflammatory cytokine and ROS in association with activation of Th1 and Th17 cells by DCs. These results collectively suggest that down-regulated IL-37 may be involved in the pathogenesis of BD.
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