Open AccessOpposite effects of miR-155 in the initial and later stages of lipopolysaccharide (LPS)-induced inflammatory response
Author(s) -
Yuhua Liu,
Xiaopeng Wan,
Yuan Yuan,
Jingjing Huang,
Yueyang Jiang,
Kaiyue Zhao,
Yan Wang,
Yang Liu,
Qingqing Wang,
Hongchuan Jin
Publication year - 2021
Publication title -
journal of zhejiang university. science b
Language(s) - English
Resource type - Journals
eISSN - 1862-1783
pISSN - 1673-1581
DOI - 10.1631/jzus.b2000826
Subject(s) - suppressor of cytokine signaling 1 , tlr4 , mediator , lipopolysaccharide , inflammation , microbiology and biotechnology , microrna , signal transduction , cytokine , biology , innate immune system , toll like receptor , immune system , cancer research , immunology , gene , suppressor , genetics
Although microRNA-155 (miR-155) is considered a pro-inflammatory mediator, cumulative evidence indicates that it also has anti-inflammatory effects in macrophages and dendritic cells. In this study, we identified the dramatic expression changes of more than half of potential miR-155-targeted genes upon lipopolysaccharide (LPS) stimulation; 223 genes were down-regulated and 85 genes were up-regulated, including suppressor of cytokine signaling 1 ( SOCS1 ) and transforming growth factor-β-activated kinase 1-binding protein 2 ( TAB2 ), two well-known genes involved in miR-155-mediated regulation of the Toll-like receptor 4 (TLR4) signaling pathway. We also found that miR-155 acted as an anti-inflammatory mediator in the initial stage of LPS-induced inflammatory response mainly through repressing TAB2 protein translation, and as a pro-inflammatory mediator by down-regulating SOCS1 in the later stage. Meanwhile, overexpression of TAB2 3' untranslated region (UTR) in macrophages promoted the development of endotoxin tolerance by competing for binding with miR-155, which resulted in an elevated expression level of SOCS1 protein. These findings provide new insights for understanding the regulatory mechanisms in fine-tuning of LPS-induced innate immune response.