Inflammasome-independent role of NLRP12 in suppressing colonic inflammation regulated by Blimp-1

Oncotarget. 2016 May 24;7(21):30575-84. doi: 10.18632/oncotarget.8872.

Abstract

NLRP12 is a member of the Nod-like receptor (NLR). Previous studies have reported enhanced colitis-associated inflammatory responses in NLRP12-deficient mice. In this study, we sought to investigate the role of NLRP12 in DSS-stimulated proinflammatory response in dendritic cells and mice colitis, and the molecular mechanisms involved in the development of the inflammation. Our results showed that down-regulation of NLRP12 is required for DSS-induced release of proinflammatory cytokines IL-1β and TNF-α; that PR domain zinc finger protein 1 (also known as Blimp-1) induces NLRP12 down-regulation during DSS-induced proinflammatory response and colitis; and that TLR4 is implicated in the up-regulation of Blimp-1 that led to the down-regulation of NLRP12 expression in DSS-induced colitis. Taken together, the results suggest that the TLR4-Blimp-1 axis promotes DSS induced experimental colitis through the down-regulation of NLRP12.

Keywords: Blimp-1; NLRP12; TLR4; colitis; inflammation.

MeSH terms

  • Animals
  • Blotting, Western
  • Cells, Cultured
  • Colitis / chemically induced
  • Colitis / genetics
  • Colitis / metabolism*
  • Dextran Sulfate
  • Humans
  • Inflammasomes / genetics
  • Inflammasomes / metabolism*
  • Interleukin-1beta / metabolism
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Male
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Positive Regulatory Domain I-Binding Factor 1 / genetics
  • Positive Regulatory Domain I-Binding Factor 1 / metabolism*
  • RNA Interference
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Inflammasomes
  • Interleukin-1beta
  • Intracellular Signaling Peptides and Proteins
  • NLRP12 protein, mouse
  • Prdm1 protein, mouse
  • Tlr4 protein, mouse
  • Toll-Like Receptor 4
  • Tumor Necrosis Factor-alpha
  • Dextran Sulfate
  • Positive Regulatory Domain I-Binding Factor 1