Enhanced interferon-γ gene expression in T cells and reduced ovalbumin-dependent lung eosinophilia in hypoxia-inducible factor-1-α- deficient mice

Jia Guo, Wenju Lu, Larissa Shimoda, Gregg L Semenza, Steve N. Georas

Research output: Contribution to journalArticle

Abstract

Background: There is growing evidence that hypoxia-inducible transcription factors are involved in the pathophysiology of asthma. Hypoxia-inducible factor-1α (HIF-1α) in particular controls the expression of many hypoxia regulated genes, but whether HIF-1α directly contributes to allergen-driven immune responses is not known. Methods: Partially HIF-1α-deficient mice (HIF-1α+/-) or wild-type littermate controls were used in all experiments. Spleen CD4+ T cells were stimulated with anti-CD3 plus anti-CD28 antibodies and cytokine secretion was measured in vitro. Mice were sensitized by intraperitoneal injection of ovalbumin (Ova) plus alum, and then challenged by intranasal Ova followed by bronchoalveolar lavage (BAL) and isolation of spleen cells. BAL cells were counted and the differential determined using cytospin, and splenocytes were incubated with Ova to measure recall cytokine production. Results: Interferon-γ secretion was significantly higher in anti-CD3 plus anti-CD28 stimulated CD4+ T cells obtained from HIF-1α+/- mice compared to wild-type controls. HIF-1α+/- mice were protected from lung eosinophilia 72 h after allergen challenge, in association with enhanced secretion of interferon-γ in recall responses of splenocytes. Conclusions: HIF-1α contributes to allergic immune responses and lung eosinophilia in a mouse model of asthma.

Original languageEnglish (US)
Pages (from-to)98-102
Number of pages5
JournalInternational Archives of Allergy and Immunology
Volume149
Issue number2
DOIs
StatePublished - May 2009

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Hypoxia-Inducible Factor 1
Ovalbumin
Eosinophilia
Interferons
T-Lymphocytes
Gene Expression
Lung
Bronchoalveolar Lavage
Allergens
Spleen
Asthma
Cytokines
Cell Hypoxia
Cell Separation
Intraperitoneal Injections
Anti-Idiotypic Antibodies
Transcription Factors
Genes

Keywords

  • Asthma mouse model
  • Gene regulation
  • Hypoxia
  • Transcription Factors

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

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title = "Enhanced interferon-γ gene expression in T cells and reduced ovalbumin-dependent lung eosinophilia in hypoxia-inducible factor-1-α- deficient mice",
abstract = "Background: There is growing evidence that hypoxia-inducible transcription factors are involved in the pathophysiology of asthma. Hypoxia-inducible factor-1α (HIF-1α) in particular controls the expression of many hypoxia regulated genes, but whether HIF-1α directly contributes to allergen-driven immune responses is not known. Methods: Partially HIF-1α-deficient mice (HIF-1α+/-) or wild-type littermate controls were used in all experiments. Spleen CD4+ T cells were stimulated with anti-CD3 plus anti-CD28 antibodies and cytokine secretion was measured in vitro. Mice were sensitized by intraperitoneal injection of ovalbumin (Ova) plus alum, and then challenged by intranasal Ova followed by bronchoalveolar lavage (BAL) and isolation of spleen cells. BAL cells were counted and the differential determined using cytospin, and splenocytes were incubated with Ova to measure recall cytokine production. Results: Interferon-γ secretion was significantly higher in anti-CD3 plus anti-CD28 stimulated CD4+ T cells obtained from HIF-1α+/- mice compared to wild-type controls. HIF-1α+/- mice were protected from lung eosinophilia 72 h after allergen challenge, in association with enhanced secretion of interferon-γ in recall responses of splenocytes. Conclusions: HIF-1α contributes to allergic immune responses and lung eosinophilia in a mouse model of asthma.",
keywords = "Asthma mouse model, Gene regulation, Hypoxia, Transcription Factors",
author = "Jia Guo and Wenju Lu and Larissa Shimoda and Semenza, {Gregg L} and Georas, {Steve N.}",
year = "2009",
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language = "English (US)",
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T1 - Enhanced interferon-γ gene expression in T cells and reduced ovalbumin-dependent lung eosinophilia in hypoxia-inducible factor-1-α- deficient mice

AU - Guo, Jia

AU - Lu, Wenju

AU - Shimoda, Larissa

AU - Semenza, Gregg L

AU - Georas, Steve N.

PY - 2009/5

Y1 - 2009/5

N2 - Background: There is growing evidence that hypoxia-inducible transcription factors are involved in the pathophysiology of asthma. Hypoxia-inducible factor-1α (HIF-1α) in particular controls the expression of many hypoxia regulated genes, but whether HIF-1α directly contributes to allergen-driven immune responses is not known. Methods: Partially HIF-1α-deficient mice (HIF-1α+/-) or wild-type littermate controls were used in all experiments. Spleen CD4+ T cells were stimulated with anti-CD3 plus anti-CD28 antibodies and cytokine secretion was measured in vitro. Mice were sensitized by intraperitoneal injection of ovalbumin (Ova) plus alum, and then challenged by intranasal Ova followed by bronchoalveolar lavage (BAL) and isolation of spleen cells. BAL cells were counted and the differential determined using cytospin, and splenocytes were incubated with Ova to measure recall cytokine production. Results: Interferon-γ secretion was significantly higher in anti-CD3 plus anti-CD28 stimulated CD4+ T cells obtained from HIF-1α+/- mice compared to wild-type controls. HIF-1α+/- mice were protected from lung eosinophilia 72 h after allergen challenge, in association with enhanced secretion of interferon-γ in recall responses of splenocytes. Conclusions: HIF-1α contributes to allergic immune responses and lung eosinophilia in a mouse model of asthma.

AB - Background: There is growing evidence that hypoxia-inducible transcription factors are involved in the pathophysiology of asthma. Hypoxia-inducible factor-1α (HIF-1α) in particular controls the expression of many hypoxia regulated genes, but whether HIF-1α directly contributes to allergen-driven immune responses is not known. Methods: Partially HIF-1α-deficient mice (HIF-1α+/-) or wild-type littermate controls were used in all experiments. Spleen CD4+ T cells were stimulated with anti-CD3 plus anti-CD28 antibodies and cytokine secretion was measured in vitro. Mice were sensitized by intraperitoneal injection of ovalbumin (Ova) plus alum, and then challenged by intranasal Ova followed by bronchoalveolar lavage (BAL) and isolation of spleen cells. BAL cells were counted and the differential determined using cytospin, and splenocytes were incubated with Ova to measure recall cytokine production. Results: Interferon-γ secretion was significantly higher in anti-CD3 plus anti-CD28 stimulated CD4+ T cells obtained from HIF-1α+/- mice compared to wild-type controls. HIF-1α+/- mice were protected from lung eosinophilia 72 h after allergen challenge, in association with enhanced secretion of interferon-γ in recall responses of splenocytes. Conclusions: HIF-1α contributes to allergic immune responses and lung eosinophilia in a mouse model of asthma.

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