| Interleukin-23 production in dendritic cells is negatively regulated by protein phosphatase 2A. | |
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MedLine Citation:
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PMID: 20404153 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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IL-12 and IL-23 are produced by activated antigen-presenting cells but the two induce distinct immune responses by promoting Th1 and Th17 cell differentiation, respectively. IL-23 is a heterodimeric cytokine consisting of two subunits: p40 that is shared with IL-12 and p19 unique to IL-23. In this study, we showed that the production of IL-23 but not IL-12 was negatively regulated by protein phosphatase 2A (PP2A) in dendritic cells (DC). PP2A inhibits IL-23 production by suppressing the expression of the IL-23p19 gene. Treating DC with okadaic acid that inhibits the PP2A activity or knocking down the catalytic subunit of PP2A with siRNA enhanced IL-23 but not IL-12 production. Unlike PP2A, MAP kinase phosphatase-1 or CYLD did not show an effect on IL-23 production supporting the specificity of PP2A. PP2A-mediated inhibition requires a newly made protein that is likely responsible for bringing PP2A and IKKbeta together upon LPS stimulation, which then results in the termination of IKK phosphorylation. Thus, our results uncovered an important role of the protein phosphatase in the regulation of IL-23 production and identified PP2A as a previously uncharacterized inhibitor of IL-23p19 expression in DC. |
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Authors:
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JiHoon Chang; Timothy J Voorhees; Yusen Liu; Yongge Zhao; Cheong-Hee Chang |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-04-19 |
Journal Detail:
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Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 107 ISSN: 1091-6490 ISO Abbreviation: Proc. Natl. Acad. Sci. U.S.A. Publication Date: 2010 May |
Date Detail:
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Created Date: 2010-05-05 Completed Date: 2010-06-08 Revised Date: 2010-11-05 |
Medline Journal Info:
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Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: United States |
Other Details:
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Languages: eng Pagination: 8340-5 Citation Subset: IM |
Affiliation:
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Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cells, Cultured Dendritic Cells / immunology*, metabolism Down-Regulation* Dual Specificity Phosphatase 1 / deficiency, metabolism I-kappa B Kinase / metabolism Interleukin-12 / biosynthesis, immunology Interleukin-23 Subunit p19 / biosynthesis, genetics, immunology* Lipopolysaccharides / immunology Mice Mice, Inbred BALB C Mice, Inbred C57BL Phosphorylation Protein Binding Protein Phosphatase 2 / genetics, metabolism* RNA, Small Interfering / genetics |
| Grant Support | |
ID/Acronym/Agency:
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AI057798/AI/NIAID NIH HHS; AI070448/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Il23a protein, mouse; 0/Interleukin-23 Subunit p19; 0/Lipopolysaccharides; 0/RNA, Small Interfering; 187348-17-0/Interleukin-12; EC 2.7.11.10/I-kappa B Kinase; EC 3.1.3.16/Protein Phosphatase 2; EC 3.1.3.48/Dual Specificity Phosphatase 1; EC 3.1.3.48/Dusp1 protein, mouse |
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