Oxidant stress responses in influenza virus pneumonia: Gene expression and transcription factor activation

Augustine M K Choi, Katharine Knobil, Sherrie L. Otterbein, Deborah A. Eastman, David Jacoby

Research output: Contribution to journalArticle

88 Citations (Scopus)

Abstract

The pathogenesis of influenza virus infections of the lungs is in part mediated by oxidative stress. Such infections might therefore be expected to induce expression of stress-response genes and genes encoding antioxidant enzymes and to activate transcriptional regulatory proteins. Mice (C57B1/6 and C3H/HeJ) were infected intranasally with influenza virus A/PR78/34 (H1N1). Expression of the genes encoding the antioxidant enzymes manganese superoxide dismutase (Mn-SOD), indoleamine-2,3-dioxygenase (IDO), heme oxygenase-1, and glutathione peroxidase were increased in the lungs of virus- infected animals. Cu/ZnSOD and catalase mRNA were not induced by viral infection. Activation of the transcriptional regulatory proteins AP-1, C/EBP, and NF-κB (which are known to be affected by oxidant stress) was demonstrated by electrophoretic mobility shift assay after vital infection. In the case of MnSOD, despite increased gene expression enzyme activity was not increased. In contrast, for heine oxygenase-1 both mRNA and activity were increased. C3H/HeJ and C57B1/6 mice, which are known to have different responses to other types of oxidant stress, also differed in their responses to viral infection. Induction of heme oxygenase-1 expression was greater in C57B1/6 mice than in C3H/HeJ mice, although inhibiting this enzyme did not alter virus-induced mortality. In contrast, IDO was more strongly induced in C3H/HeJ mice. Activation of NF-κB was much more marked in C57B1/6 mice than in C3H/HeJ mice. Although virus replication and inflammatory responses were equivalent in the two strains, lung injury (as measured by wet-to-dry wt ratios) and mortality were greater in C3H/HeJ mice than in C57B1/6 mice, a difference that may be related to differing oxidant stress responses. Thus influenza pneumonia causes an oxidant stress response in the lungs, the nature of which is determined in part by the genetic background of the host.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume271
Issue number3 15-3
StatePublished - Sep 1996
Externally publishedYes

Fingerprint

Orthomyxoviridae
Oxidants
Inbred C3H Mouse
Transcriptional Activation
Pneumonia
Transcription Factors
Gene Expression
Virus Diseases
Heme Oxygenase-1
Enzymes
Lung
Antioxidants
Indoleamine-Pyrrole 2,3,-Dioxygenase
Viruses
Dioxygenases
Oxygenases
Messenger RNA
Mortality
Influenza A virus
Transcription Factor AP-1

Keywords

  • activator protein-1
  • heme oxygenase-1
  • indoleamine-2,3- dioxygenase
  • nuclear factor-κB
  • superoxide dismutase

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Cell Biology
  • Physiology
  • Physiology (medical)

Cite this

Oxidant stress responses in influenza virus pneumonia : Gene expression and transcription factor activation. / Choi, Augustine M K; Knobil, Katharine; Otterbein, Sherrie L.; Eastman, Deborah A.; Jacoby, David.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 271, No. 3 15-3, 09.1996.

Research output: Contribution to journalArticle

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