MiR-150 impairs inflammatory cytokine production by targeting ARRB-2 after blocking CD28/B7 costimulatory pathway
Document Type
Article
Publication Date
2016
Abstract
Abstract MiR-150, a major modulator negatively regulating the development and differentiation of various immune cells, is widely involved in orchestrating inflammation. In transplantation immunity, miR-150 can effectively induce immune tolerance, although the underlying mechanisms have not been fully elucidated. In the current study, we found that miR-150 is elevated after blocking CD28/B7 co-stimulatory signaling pathway and impaired IL-2 production by targeting ARRB2. Further investigation suggested that miR-150 not only repressed the level of ARRB2/PDE4 directly but also prevented AKT/ARRB2/PDE4 trimer recruitment into the lipid raft by inhibiting the activities of PI3K and AKT through the cAMP-PKA-Csk signaling pathway. This leads to the interruption of cAMP degradation and subsequently results in inhibition of the NF-kB pathway and reduced production of both IL-2 and TNF. In conclusion, our study demonstrated that miR-150 can effectively prevent CD28/B7 co-stimulatory signaling transduction, decrease production of inflammatory cytokines, such as IL-2 and TNF, and elicit the induction of immune tolerance. Therefore, miR-150 could become a novel potential therapeutic target in transplantation immunology.
Publication Title
Immunology letters
Volume
172
First Page
1
Last Page
10
Recommended Citation
Sand, Wei; Wang, Ying; Zhang, Cong; Zhang, Dianzheng; Sun, Cai; Niu, Mingshan; Zhang, Zhe; Wei, Xiangyu; Pan, Bin; and al., et, "MiR-150 impairs inflammatory cytokine production by targeting ARRB-2 after blocking CD28/B7 costimulatory pathway" (2016). PCOM Scholarly Works. 1650.
https://digitalcommons.pcom.edu/scholarly_papers/1650
Comments
This article was published in Immunology letters, Volume 172 , Pages 1-10.
The published version is available at http://dx.doi.org/10.1016/j.imlet.2015.11.001.Copyright © 2016 Elsevier.