Cigarette smoke extract-induced downregulation of p300 is responsible for the impaired inflammatory cytokine response of macrophages

Kyoung Hee Lee, Jisu Woo, Ji Yeon Kim, Chang Hoon Lee, Chul Gyu Yoo

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Patients with chronic obstructive pulmonary disease (COPD) are susceptible to infection owing to the impaired immune function of alveolar macrophages. This is presumed to be caused, at least partially, by cigarette smoke (CS), which is a major risk factor for COPD. Although CS has been reported to inhibit Toll-like receptor (TLR) function and phagocytosis in macrophages, the molecular mechanism of CS-mediated impairment of macrophage immune function has not been completely elucidated. We investigated the effects of CS extracts (CSE) on macrophage immune function and its molecular mechanism. We assessed lipopolysaccharide (LPS, TLR4 ligand)-, Pam3CSK4 (TLR2 ligand)-, or CpG-oligodeoxynucleotide (TLR9 ligand)-induced IL-6, TNF-α, and IL-1β production in macrophages. Upregulation of IL-6, TNF-α, and IL-1β mRNA and protein by TLR ligands was suppressed on treatment with CSE. However, LPS-induced MAP kinase activation, IκBα degradation, and nuclear translocation of NF-κB were not impeded by CSE. In contrast, CSE significantly suppressed NF-κB transcriptional activity in the nucleus. We found that p300, which acetylates RelA/p65 at lysine 310, and acetyl-p65 (K310) were downregulated upon CSE treatment. Knock-down of p300 suppressed LPS-induced acetylation of NF-κB p65 and production of inflammatory cytokine. To summarize, these results suggest that CSE impair cytokine response by decreasing the expression levels of p300.

Original languageEnglish
Article number110050
JournalCellular Signalling
Volume85
DOIs
StatePublished - Sep 2021
Externally publishedYes

Keywords

  • Acetyl-p65
  • Cigarette smoke extracts
  • Inflammatory cytokines
  • Macrophage
  • p300

Fingerprint

Dive into the research topics of 'Cigarette smoke extract-induced downregulation of p300 is responsible for the impaired inflammatory cytokine response of macrophages'. Together they form a unique fingerprint.

Cite this