Journal article
Intracellular thiols contribute to Th2 function via a positive role in IL-4 production
The Journal of immunology (1950), Vol.171(10), pp.5107-5115
11/15/2003
DOI: 10.4049/jimmunol.171.10.5107
PMID: 14607909
Abstract
A number of lung diseases, including many interstitial lung diseases and HIV infection, are associated with decreases in intracellular thiols. Altered Th1/Th2 T cell balance has also been associated with disease progression in many of the same diseases. IFN-gamma and IL-4 are critical effector cytokines of Th1 and Th2 cells, respectively. To determine the effect of thiols on the production of IFN-gamma and IL-4 by splenocytes, cells were incubated in the presence and the absence of N-acetylcysteine (NAC) and stimulated with alphaCD3 or alphaCD3 and IL-12. Augmenting intracellular soluble thiol pools ( approximately 2-fold) with 15 mM NAC blocked induction of IFN-gamma and increased production of IL-4 without causing significant changes in intracellular glutathione levels. The effect of NAC on IL-4 production was not linked to an increase in STAT6 phosphorylation, as STAT6 levels were decreased, nor did the increase in IL-4 occur with purified CD4 cells. We found that NAC increased splenocyte IL-4 production via an effect on APCs. We also found that NAC increased two IL-4 relevant transcription factors (AP-1) and NFATc. These studies suggest that increasing intracellular reduced thiol pools decreases IL-12 signaling and IFN-gamma production, while increasing IL-4 production. The sum of these effects may contribute to alterations in the balance between Th1 and Th2 responses in lung diseases associated alterations in intracellular thiol pools.
Details
- Title: Subtitle
- Intracellular thiols contribute to Th2 function via a positive role in IL-4 production
- Creators
- Martha M Monick - Department of Internal Medicine, University of Iowa, Roy J. and Lucille A. Carver College of Medicine, and Veterans' Administration Medical Center, Iowa City, IA 52242, USA. martha-monick@uiowa.eduLobelia SamavatiNoah S ButlerMichael MohningLinda S PowersTimur YarovinskyDouglas R SpitzGary W Hunninghake
- Resource Type
- Journal article
- Publication Details
- The Journal of immunology (1950), Vol.171(10), pp.5107-5115
- Publisher
- United States
- DOI
- 10.4049/jimmunol.171.10.5107
- PMID
- 14607909
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Grant note
- ES09607 / NIEHS NIH HHS HL51469 / NHLBI NIH HHS HL60316 / NHLBI NIH HHS CA66081 / NCI NIH HHS RR00059 / NCRR NIH HHS
- Language
- English
- Date published
- 11/15/2003
- Academic Unit
- Microbiology and Immunology; Pathology; Radiation Oncology; Internal Medicine
- Record Identifier
- 9984001123802771
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