Aerosolized Gamma Interferon (IFN-γ) Induces Expression of the Genes Encoding the IFN-γ-Inducible 10-Kilodalton Protein but Not Inducible Nitric Oxide Synthase in the Lung during Tuberculosis

Bindu Raju, Yoshihiko Hoshino, Kenichi Kuwabara, Ilana Belitskaya, Savita Prabhakar, Antony Canova, Jeffrey (Jeff) Gold, Rany Condos, Richard I. Pine, Stuart Brown, William N. Rom, Michael D. Weiden

Research output: Contribution to journalArticle

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Abstract

Gamma interferon (IFN-γ) is critical in the immune response against Mycobacterium tuberculosis. In an ongoing trial of aerosol IFN-γ in conjunction with standard drug therapy, we have observed activation of IFN signaling in bronchoalveolar lavage (BAL) cells from tuberculosis (TB) patients. We hypothesized that aerosol IFN-γ treatment of pulmonary TB would increase expression of genes important for the control of TB. We investigated the expression of downstream genes by measuring inducible nitric oxide synthase (iNOS) and the chemokine IFN-inducible 10-kDa protein (IP-10) by real-time quantitative reverse transcription-PCR. In vitro, M. tuberculosis induced IP-10, and IFN-γ stimulated this further, with no effect on iNOS expression. We studied 21 patients with pulmonary TB and 7 healthy subjects. Similar to the in vitro model, IP-10 mRNA was increased in BAL cells from TB patients and was augmented after treatment with aerosolized IFN-γ. TB was also associated with elevated iNOS mRNA, but aerosolized IFN-γ did not further enhance expression. Genomic analysis identified 1,300 of 4,058 genes expressed in BAL cells from six TB patients before and after 1 month of therapy, including aerosolized IFN-γ. However, only 15 genes were differentially regulated by IFN-γ. We conclude that iNOS and IP-10 mRNA expression is increased in TB but that aerosol IFN-γ treatment increases expression of few genes in the human lung.

Original languageEnglish (US)
Pages (from-to)1275-1283
Number of pages9
JournalInfection and Immunity
Volume72
Issue number3
DOIs
StatePublished - Mar 2004
Externally publishedYes

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Chemokine CXCL10
Nitric Oxide Synthase Type II
Interferons
Interferon-gamma
Tuberculosis
Gene Expression
Lung
Bronchoalveolar Lavage
Aerosols
Pulmonary Tuberculosis
Mycobacterium tuberculosis
Messenger RNA
Therapeutics
Chemokines
Genes
Reverse Transcription
Healthy Volunteers
Drug Therapy
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Immunology

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Aerosolized Gamma Interferon (IFN-γ) Induces Expression of the Genes Encoding the IFN-γ-Inducible 10-Kilodalton Protein but Not Inducible Nitric Oxide Synthase in the Lung during Tuberculosis. / Raju, Bindu; Hoshino, Yoshihiko; Kuwabara, Kenichi; Belitskaya, Ilana; Prabhakar, Savita; Canova, Antony; Gold, Jeffrey (Jeff); Condos, Rany; Pine, Richard I.; Brown, Stuart; Rom, William N.; Weiden, Michael D.

In: Infection and Immunity, Vol. 72, No. 3, 03.2004, p. 1275-1283.

Research output: Contribution to journalArticle

Raju, Bindu ; Hoshino, Yoshihiko ; Kuwabara, Kenichi ; Belitskaya, Ilana ; Prabhakar, Savita ; Canova, Antony ; Gold, Jeffrey (Jeff) ; Condos, Rany ; Pine, Richard I. ; Brown, Stuart ; Rom, William N. ; Weiden, Michael D. / Aerosolized Gamma Interferon (IFN-γ) Induces Expression of the Genes Encoding the IFN-γ-Inducible 10-Kilodalton Protein but Not Inducible Nitric Oxide Synthase in the Lung during Tuberculosis. In: Infection and Immunity. 2004 ; Vol. 72, No. 3. pp. 1275-1283.
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AU - Raju, Bindu

AU - Hoshino, Yoshihiko

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AU - Belitskaya, Ilana

AU - Prabhakar, Savita

AU - Canova, Antony

AU - Gold, Jeffrey (Jeff)

AU - Condos, Rany

AU - Pine, Richard I.

AU - Brown, Stuart

AU - Rom, William N.

AU - Weiden, Michael D.

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AB - Gamma interferon (IFN-γ) is critical in the immune response against Mycobacterium tuberculosis. In an ongoing trial of aerosol IFN-γ in conjunction with standard drug therapy, we have observed activation of IFN signaling in bronchoalveolar lavage (BAL) cells from tuberculosis (TB) patients. We hypothesized that aerosol IFN-γ treatment of pulmonary TB would increase expression of genes important for the control of TB. We investigated the expression of downstream genes by measuring inducible nitric oxide synthase (iNOS) and the chemokine IFN-inducible 10-kDa protein (IP-10) by real-time quantitative reverse transcription-PCR. In vitro, M. tuberculosis induced IP-10, and IFN-γ stimulated this further, with no effect on iNOS expression. We studied 21 patients with pulmonary TB and 7 healthy subjects. Similar to the in vitro model, IP-10 mRNA was increased in BAL cells from TB patients and was augmented after treatment with aerosolized IFN-γ. TB was also associated with elevated iNOS mRNA, but aerosolized IFN-γ did not further enhance expression. Genomic analysis identified 1,300 of 4,058 genes expressed in BAL cells from six TB patients before and after 1 month of therapy, including aerosolized IFN-γ. However, only 15 genes were differentially regulated by IFN-γ. We conclude that iNOS and IP-10 mRNA expression is increased in TB but that aerosol IFN-γ treatment increases expression of few genes in the human lung.

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