SIRT1 regulates inflammation response of macrophages in sepsis mediated by long noncoding RNA

Biochim Biophys Acta Mol Basis Dis. 2018 Mar;1864(3):784-792. doi: 10.1016/j.bbadis.2017.12.029. Epub 2017 Dec 19.

Abstract

Molecular mechanisms for macrophage immune responses modulated by SIRT1 during sepsis remain unclear. Here, we show that SIRT1 expression is down-regulated in macrophages from mouse sepsis model or LPS stimulation. SIRT1 expression in macrophages correlates with low levels of a long noncoding RNA (lncRNA)-NONMMUT003701 [named as lncRNA-CCL2]. SIRT1 inhibits lncRNA-CCL2 expression via sustaining a repressive chromatin state in the lncRNA-CCL2 locus. The inflammation cytokines expression is downregulated by knockdown of lncRNA-CCL2. Such inhibition can be reversed partly by decreased SIRT1 activity. Thus, this work uncovers previously unidentified mechanisms in which SIRT1 associates with lncRNA and lncRNA regulates macrophage inflammatory response.

Keywords: Inflammation cytokines; Macrophages; SIRT1; Sepsis; lncRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Gene Expression Regulation
  • Inflammation / genetics*
  • Inflammation / pathology
  • Macrophages / drug effects*
  • Macrophages / immunology
  • Macrophages / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • RNA, Long Noncoding / physiology*
  • Sepsis / complications
  • Sepsis / genetics
  • Sepsis / immunology
  • Sepsis / pathology*
  • Signal Transduction / genetics
  • Sirtuin 1 / genetics
  • Sirtuin 1 / physiology*
  • Systemic Inflammatory Response Syndrome / genetics
  • Systemic Inflammatory Response Syndrome / immunology
  • Systemic Inflammatory Response Syndrome / pathology

Substances

  • RNA, Long Noncoding
  • Sirt1 protein, mouse
  • Sirtuin 1