RUVBL1/2 Complex Regulates Pro-Inflammatory Responses in Macrophages via Regulating Histone H3K4 Trimethylation

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review

4 Scopus Citations
View graph of relations

Author(s)

  • Rui Zhang
  • Chris Y. Cheung
  • Sang-Uk Seo
  • Hang Liu
  • Lakhansing Pardeshi
  • Koon Ho Wong
  • Larry M. C. Chow
  • Mary P. Chau
  • Yixiang Wang
  • Ah Ra Lee
  • Woon Yong Kwon
  • Bill Kwan-wai Chan
  • Kenneth Wong
  • Richard K. W. Choy
  • Ben C. B. Ko

Detail(s)

Original languageEnglish
Article number679184
Journal / PublicationFrontiers in Immunology
Volume12
Online published4 Jun 2021
Publication statusPublished - Jun 2021

Link(s)

Abstract

Macrophages play an important role in the host defense mechanism. In response to infection, macrophages activate a genetic program of pro-inflammatory response to kill any invading pathogen, and initiate an adaptive immune response. We have identified RUVBL2 - an ATP-binding protein belonging to the AAA+ (ATPase associated with diverse cellular activities) superfamily of ATPases - as a novel regulator in pro-inflammatory response of macrophages. Gene knockdown of Ruvbl2, or pharmacological inhibition of RUVBL1/2 activity, compromises type-2 nitric oxide synthase (Nos2) gene expression, nitric oxide production and anti-bacterial activity of mouse macrophages in response to lipopolysaccharides (LPS). RUVBL1/2 inhibitor similarly inhibits pro-inflammatory response in human monocytes, suggesting functional conservation of RUVBL1/2 in humans. Transcriptome analysis further revealed that major LPS-induced pro-inflammatory pathways in macrophages are regulated in a RUVBL1/2-dependent manner. Furthermore, RUVBL1/2 inhibition significantly reduced the level of histone H3K4me3 at the promoter region of Nos2 and Il6, two prototypical pro-inflammatory genes, and diminished the recruitment of NF-kappaB to the corresponding enhancers. Our study reveals RUVBL1/2 as an integral component of macrophage pro-inflammatory responses through epigenetic regulations, and the therapeutic potentials of RUVBL1/2 inhibitors in the treatment of diseases caused by aberrant activation of pro-inflammatory pathways.

Research Area(s)

  • epigenetic modulation, H3K4 trimethylation, macrophages, pro-inflammatory, RUVBL1/2

Citation Format(s)

RUVBL1/2 Complex Regulates Pro-Inflammatory Responses in Macrophages via Regulating Histone H3K4 Trimethylation. / Zhang, Rui; Cheung, Chris Y.; Seo, Sang-Uk et al.
In: Frontiers in Immunology, Vol. 12, 679184, 06.2021.

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review

Download Statistics

No data available