Altered IL-4 mRNA stability correlates with Th1 and Th2 bias and susceptibility to hypersensitivity pneumonitis in two inbred strains of mice

Noah S Butler; Martha M Monick; Timur O Yarovinsky; Linda S Powers; Gary W Hunninghake

doi:10.4049/jimmunol.169.7.3700

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Altered IL-4 mRNA stability correlates with Th1 and Th2 bias and susceptibility to hypersensitivity pneumonitis in two inbred strains of mice

Journal article

Peer reviewed

Altered IL-4 mRNA stability correlates with Th1 and Th2 bias and susceptibility to hypersensitivity pneumonitis in two inbred strains of mice

Noah S Butler, Martha M Monick, Timur O Yarovinsky, Linda S Powers and Gary W Hunninghake

The Journal of immunology (1950), Vol.169(7), pp.3700-3709

10/01/2002

DOI: 10.4049/jimmunol.169.7.3700

PMID: 12244163

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Abstract

Previously, we have shown in a model of hypersensitivity pneumonitis that Th1-biased C57BL/6 mice are susceptible and Th2-biased DBA/2 mice are resistant to disease. We also showed that this was explained in part by differential regulation of IL-12 by IL-4. For these reasons, we postulated that C57BL/6 and DBA/2 mice differentially express IL-4. In this study, we show that C57BL/6 immune cells express Th2 but not Th1 cytokines at lower levels than DBA/2 cells. We also found that C57BL/6 splenocytes exhibit decreased mRNA stability of Th2 cytokines, relative to DBA/2 splenocytes. Stability of IL-2 and IFN-gamma were similar in the two strains of mice. Differences in Th2 cytokine mRNA stability between C57BL/6 and DBA/2 cells were not due to sequence polymorphism at specific regions of the IL-4/IL-13 locus. Furthermore, expression of Th1- and Th2-specific transcription factors T-bet and GATA-3, as well as the nuclear factor of activated T cells transcription factor, NFATc, was not significantly different between the two mice. Our data suggest that decreased mRNA stability of Th2 cytokines in C57BL/6 splenocytes may underlie the differential susceptibility to hypersensitivity pneumonitis between C57BL/6 and DBA/2 mice. Moreover, our results indicate that regulation of mRNA stability may serve as an important mechanism underlying Th1/Th2 immune polarization.

RNA Stability - immunology

Spleen - immunology

Th2 Cells - immunology

Lung - cytology

RNA, Messenger - metabolism

Th1 Cells - immunology

CD4-Positive T-Lymphocytes - immunology

DNA-Binding Proteins - metabolism

Th1 Cells - metabolism

Interleukin-4 - biosynthesis

Interleukin-4 - pharmacology

Disease Susceptibility - immunology

Female

Mice, Inbred DBA

Lung - metabolism

Trans-Activators - biosynthesis

Interleukin-4 - genetics

GATA3 Transcription Factor

Alveolitis, Extrinsic Allergic - immunology

Base Sequence - genetics

Interleukin-4 - metabolism

Mice, Inbred C57BL

CD4-Positive T-Lymphocytes - metabolism

Cells, Cultured

Polymorphism, Genetic - immunology

Immunophenotyping

Th2 Cells - cytology

Transcription Factors - biosynthesis

Spleen - cytology

NFATC Transcription Factors

Genetic Markers - immunology

Th2 Cells - metabolism

Nuclear Proteins

Transcription Factors - metabolism

Animals

Spleen - metabolism

Lymphocyte Count

Trans-Activators - metabolism

Alveolitis, Extrinsic Allergic - metabolism

Mice

Th1 Cells - cytology

Kinetics

DNA-Binding Proteins - biosynthesis

T-Box Domain Proteins

Lung - immunology

Details

Title: Subtitle: Altered IL-4 mRNA stability correlates with Th1 and Th2 bias and susceptibility to hypersensitivity pneumonitis in two inbred strains of mice
Creators: Noah S Butler - Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Iowa College of Medicine and Veterans Administration Medical Center, Iowa City, IA 52242, USA. noah-butler@uiowa.edu
Martha M Monick
Timur O Yarovinsky
Linda S Powers
Gary W Hunninghake
Resource Type: Journal article
Publication Details: The Journal of immunology (1950), Vol.169(7), pp.3700-3709
DOI: 10.4049/jimmunol.169.7.3700
PMID: 12244163
NLM abbreviation: J Immunol
ISSN: 0022-1767
eISSN: 1550-6606
Publisher: United States
Grant note: E509607 / PHS HHS RR00059 / NCRR NIH HHS
Language: English
Date published: 10/01/2002
Academic Unit: Microbiology and Immunology; Internal Medicine
Record Identifier: 9984002373802771

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