Interleukin-4 suppresses the expression of macrophage NADPH oxidase heavy chain subunit (gp91-phox)

Yaling Zhou, Gaofeng Lin, Michael P Murtaugh

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

The production of superoxide anion by NADPH oxidase is a principal nonspecific bactericidal activity of macrophages and neutrophils in host defense. However, exuberant production of superoxide anion also damages host tissues. Cloning and DNA sequencing of the 91 kDa subunit (gp91-phox) open reading frame indicated a high degree of sequence conservation, greater than 90% in nucleotide and amino acid sequences, between the porcine and human cDNAs. We show in pigs that interleukin-4 (IL-4), a T lymphocyte cytokine which plays a major role in mediating antibody responses to pathogens, suppresses superoxide anion production in macrophages by specifically reducing the level of mRNA encoding gp91-phox. Messenger RNA levels are suppressed approx. 70% within 4 h and persist for 24 h without any change in the rate of mRNA turnover. Nuclear run-on analysis showed that IL-4 did not alter the rate of gp91-phox gene transcription under conditions in which IL-1β transcription was inhibited. These results indicate that IL-4 suppresses the inflammatory response of macrophages by mechanisms that include post-transcriptional regulation of the 91 kDa catalytic subunit of NADPH oxidase, and transcriptional regulation of inflammatory cytokine expression.

Original languageEnglish (US)
Pages (from-to)40-48
Number of pages9
JournalBBA - Molecular Cell Research
Volume1265
Issue number1
DOIs
StatePublished - Feb 16 1995

Keywords

  • (Swine)
  • Interleukin-4
  • Macrophage
  • NADPH oxidase
  • gp91-phox

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