Hypercapnia selectively modulates LPS-induced changes in innate immune and DNA replication-related gene transcription in the macrophage

S. Marina Casalino-Matsuda*, Sergejs Berdnikovs, Naizhen Wang, Aisha Nair, Khalilah L. Gates, Greg J. Beitel, Peter H.S. Sporn

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Hypercapnia, the elevation of CO 2 in blood and tissues, commonly occurs in severe acute and chronic respiratory diseases and is associated with increased risk of death. Recent studies have shown that hypercapnia inhibits expression of select innate immune genes and suppresses host defence against bacterial and viral pneumonia in mice. In the current study, we evaluated the effect of culture under conditions of hypercapnia (20% CO 2) versus normocapnia (5% CO 2), both with normoxia, on global gene transcription in human THP-1 and mouse RAW 264.7 macrophages stimulated with lipopolysaccharide (LPS). We found that hypercapnia selectively downregulated transcription of LPS-induced genes associated with innate immunity, antiviral response, type I interferon signalling, cytokine signalling and other inflammatory pathways in both human and mouse macrophages. Simultaneously, hypercapnia increased expression of LPS-downregulated genes associated with mitosis, DNA replication and DNA repair. These CO 2 -induced changes in macrophage gene expression help explain hypercapnic suppression of antibacterial and antiviral host defence in mice and reveal a mechanism that may underlie, at least in part, the high mortality of patients with severe lung disease and hypercapnia.

Original languageEnglish (US)
Article number20200039
JournalInterface Focus
Volume11
Issue number2
DOIs
StatePublished - Apr 6 2021

Keywords

  • CO 2
  • gene expression
  • hypercapnia
  • innate immunity
  • lipopolysaccharide
  • macrophage

ASJC Scopus subject areas

  • Biotechnology
  • Biophysics
  • Bioengineering
  • Biochemistry
  • Biomaterials
  • Biomedical Engineering

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