Open AccessmiR‐181a and miR‐150 regulate dendritic cell immune inflammatory responses and cardiomyocyte apoptosis via targeting JAK 1– STAT 1/c‐Fos pathway
Author(s) -
Zhu Jianbing,
Yao Kang,
Guo Junjie,
Shi Hongtao,
Ma Leilei,
Wang Qian,
Liu Haibo,
Gao Wei,
Sun Aijun,
Zou Yunzeng,
Ge Junbo
Publication year - 2017
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13201
Subject(s) - microbiology and biotechnology , immune system , inflammation , biology , jak stat signaling pathway , gene silencing , cytokine , signal transduction , stat , tumor necrosis factor alpha , apoptosis , proinflammatory cytokine , cancer research , immunology , stat3 , tyrosine kinase , biochemistry , gene
The immune inflammatory response plays a crucial role in many cardiac pathophysiological processes, including ischaemic cardiac injury and the post‐infarction repair process. Micro RNA s (mi RNA s) regulate the development and function of dendritic cells ( DC s), which are key players in the initiation and regulation of immune responses; however, the underlying regulatory mechanisms remain unclear. Here, we used the supernatants of necrotic primary cardiomyocytes (Necrotic‐S) to mimic the myocardial infarction ( MI ) microenvironment to investigate the role of mi RNA s in the regulation of DC ‐mediated inflammatory responses. Our results showed that Necrotic‐S up‐regulated the DC maturation markers CD 40, CD 83 and CD 86 and increased the production of inflammatory cytokines, concomitant with the up‐regulation of miR‐181a and down‐regulation of miR‐150. Necrotic‐S stimulation activated the JAK / STAT pathway and promoted the nuclear translocation of c‐Fos and NF ‐κB p65, and silencing of STAT 1 or c‐Fos suppressed Necrotic‐S‐induced DC maturation and inflammatory cytokine production. The effects of Necrotic‐S on DC maturation and inflammatory responses, its activation of the JAK / STAT pathway and the induction of cardiomyocyte apoptosis under conditions of hypoxia were suppressed by miR‐181a or miR‐150 overexpression. Taken together, these data indicate that miR‐181a and miR‐150 attenuate DC immune inflammatory responses via JAK 1– STAT 1/c‐Fos signalling and protect cardiomyocytes from cell death under conditions of hypoxia.