Author:
Liang Liang,Zhou Qingyun,Feng Lujia
Abstract
Abstract
Background
Earlier, we reported that the microRNA (miR)-155 expression in dendritic cells (DCs) from Behcet’s disease (BD) patients was decreased and affected cytokine production of DCs. In this study, we investigated the mechanisms whereby miR-155 regulates cytokine production by DCs.
Methods
The formation of autophagosomes in DCs was detected by transmission electron microscopy. Western blotting was used to detect the protein levels of LC3, Beclin-1, P62, p-mTOR, and p-Akt in DCs. TNF-α, IL-6, and IL-1β expression were investigated by ELISA. MiR-155 mimics were transfected to DCs to evaluate its effects on autophagy and cytokine production. RNA interference was used to downregulate the expression of TAB2.
Results
The formation of autophagosomes was found in DCs of active BD patients. The expressions of LC3-II, Beclin-1, and P62 were significantly increased in DCs of active BD patients compared to that of inactive BD patients and healthy controls. The expressions of IL-6, IL-1β, and TNF-α were significantly increased in DCs of active BD patients compared to that of healthy controls. The autophagy promoter (3-MA) and inhibitor (rapamycin) significantly decreased or increased the expression of TNF-α, IL-6, and IL-1β by DCs. The expression of LC3-II and Beclin-1 was significantly increased, but the expression of P62 proteins was decreased in DCs transfected with miR-155 mimics or after TAB2 was downregulated. The expression of TNF-α, IL-6, and IL-1β was decreased in DCs after miR-155 was upregulated or TAB2 was downregulated. The ratios of p-Akt/Akt and p-mTOR/mTOR were decreased in DCs after miR-155 was upregulated.
Conclusions
These results suggest that miR-155 affects the production of TNF-α, IL-6, and IL-1β by DCs through activation of the Akt/mTOR signaling pathway and by affecting the process of autophagy.
Funder
Basic Research program of Chongqing
Natural Science Foundation Major International (Regional) Joint Research Project
Natural Science Foundation Project of Chongqing
Chongqing Key Laboratory of Ophthalmology
Chongqing Science & Technology Platform and Base Construction Program
the Science and Technology Project Foundation of Chongqing
National Natural Science Foundation Project
Publisher
Springer Science and Business Media LLC
Cited by
11 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献