Format

Send to:

Choose Destination
See comment in PubMed Commons below
J Allergy Clin Immunol. 2005 Sep;116(3):550-7.

Respiratory syncytial virus infection in the absence of STAT 1 results in airway dysfunction, airway mucus, and augmented IL-17 levels.

Author information

  • 1Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232-2650, USA.

Abstract

BACKGROUND:

Respiratory syncytial virus (RSV) is the leading infectious cause of respiratory failure and wheezing in infants and young children. Prematurity is the greatest risk factor for severe RSV-induced disease, and recent studies suggest that premature children have lower levels of the type I IFNs (alpha/beta), for which signal transducer and activator of transcription (STAT) 1 is a critical intracellular signaling molecule.

OBJECTIVE:

We hypothesized that RSV infection in STAT 1 knockout (STAT 1 KO) mice would result in both increased airway resistance and airway hyperresponsiveness.

METHODS:

Wild-type (WT) and STAT 1 KO mice on a BALB/c background were either RSV or mock infected. Phenotypic response to infection was assessed by means of plethysmography, immunohistochemistry, and lung cytokine measurement.

RESULTS:

We found that STAT 1 KO mice infected with RSV (STAT 1 KO-RSV) had greater baseline lung resistance (P=.05) and airway responsiveness (P<.001) than mock-infected STAT 1 KO (STAT 1 KO-MOCK), RSV-infected wild type (WT-RSV), and mock-infected wild type (WT-MOCK) mice. In addition, the STAT 1 KO-RSV mice showed induction of mucus production and expression of gob-5 and Muc5ac, conditions not present in any of the other 3 groups. IL-17, a cytokine that regulates Muc5ac expression, was expressed in the lungs of the STAT 1 KO-RSV mice, whereas lung levels of IL-17 were undetectable in the remaining groups. Expression of the IL-23-specific p19 subunit was also increased in the STAT 1 KO-RSV mice but not in the WT-RSV mice.

CONCLUSION:

These results show that STAT 1 has an important regulatory role in RSV-induced alteration of airway function.

PMID:
16159623
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Write to the Help Desk