LncRNA MIAT downregulates IL-1β, TNF-ɑ to suppress macrophage inflammation but is suppressed by ATP-induced NLRP3 inflammasome activation

Cell Cycle. 2021 Jan;20(2):194-203. doi: 10.1080/15384101.2020.1867788. Epub 2021 Jan 18.

Abstract

Cardiovascular disease (CVD) has been identified as the leading cause of premature deaths in rheumatoid arthritis (RA), accounting for about 40 to 50% of all deaths. Macrophage inflammation is regarded as a key point to link to the two diseases. Recently, long non-coding RNAs (lncRNAs) have acknowledged as a regulator of inflammation significantly. Here, we firstly found that lncRNA myocardial infarction associated transcript (lncRNA MIAT), a crucial lncRNA to regulate CVD, expressed increasingly in synovium and myocardial tissues of collagen-induced arthritis (CIA) mice. Besides, we also verified that the increased infiltration of macrophage occurred in those tissues of the CIA. In vitro, we found that macrophage inflammation induced by LPS could up-regulate lncRNA MIAT expression. LncRNA MIAT seemed to inhibit the expression of IL-1β, TNF-ɑ and be suppressed by ATP-induced NLRP3 inflammasome activation pathway. Therefore, these data indicated an anti-inflammatory effect of lncRNA MIAT in macrophage and an original research direction for high cardiovascular risk in RA.

Keywords: Long non-coding RNA MIAT; inflammation; macrophages.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Inflammasomes / metabolism*
  • Inflammation / metabolism
  • Interleukin-1beta / metabolism*
  • Macrophages / metabolism*
  • Mice
  • NLR Family, Pyrin Domain-Containing 3 Protein / genetics
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • RNA, Long Noncoding / genetics*
  • Signal Transduction / physiology
  • Tumor Necrosis Factor-alpha / metabolism*

Substances

  • IL1B protein, mouse
  • Inflammasomes
  • Interleukin-1beta
  • Miat long non-coding RNA
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, mouse
  • RNA, Long Noncoding
  • Tumor Necrosis Factor-alpha

Grants and funding

This work was supported by the National Natural Science Foundation of China [81201060]; National Natural Science Foundation of China [81201060].