| The regulation of Th1 responses by the p38 MAPK. | |
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MedLine Citation:
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PMID: 20937847 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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IL-12 is a dimeric cytokine that is produced primarily by APCs. In this study we examined the role that the p38 MAPKs (MAPK/p38) play in regulating IL-12 production. We show that inhibition of p38 dramatically increased IL-12 production upon stimulation, while decreasing TNF-α. This reciprocal effect on these two cytokines following MAPK/p38 inhibition occurred in many different APCs, following a variety of different stimuli. IL-12 production was also increased in macrophages treated with small interfering RNA to limit p38α expression, and in macrophages deficient in MKK3, a kinase upstream of p38. The increase in IL-12 production following MAPK/p38 inhibition appears to be due to enhanced IL-12 (p40) mRNA stability. We show that MAPK/p38 inhibition can promote Th1 immune responses and thereby enhance vaccine efficacy against leishmaniasis. In a mouse model of Leishmania major infection, vaccination with heat-killed L. major plus CpG and SB203580 elicited complete protection against infection compared with heat-killed L. major plus CpG without SB203580. Thus, this work suggests that MAPK/p38 inhibitors may be applied as adjuvants to bias immune responses and improve vaccinations against intracellular pathogens. |
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Authors:
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Ziyan Yang; Xia Zhang; Patricia A Darrah; David M Mosser |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-10-11 |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 185 ISSN: 1550-6606 ISO Abbreviation: J. Immunol. Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-11-04 Completed Date: 2010-12-02 Revised Date: 2011-09-26 |
Medline Journal Info:
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Nlm Unique ID: 2985117R Medline TA: J Immunol Country: United States |
Other Details:
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Languages: eng Pagination: 6205-13 Citation Subset: AIM; IM |
Affiliation:
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Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antigen-Presenting Cells / immunology, metabolism Blotting, Western Enzyme Inhibitors / pharmacology Gene Expression Regulation / immunology* Imidazoles / pharmacology Interleukin-12 / biosynthesis*, immunology Leishmaniasis / immunology, prevention & control Leishmaniasis Vaccines / immunology* Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Knockout Pyridines / pharmacology RNA, Small Interfering Reverse Transcriptase Polymerase Chain Reaction Transfection Tumor Necrosis Factor-alpha / biosynthesis, immunology p38 Mitogen-Activated Protein Kinases / immunology, metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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AI55576/AI/NIAID NIH HHS; R01 AI049383-10/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Enzyme Inhibitors; 0/Imidazoles; 0/Leishmaniasis Vaccines; 0/Pyridines; 0/RNA, Small Interfering; 0/SB 203580; 0/Tumor Necrosis Factor-alpha; 187348-17-0/Interleukin-12; EC 2.7.11.24/p38 Mitogen-Activated Protein Kinases |
| Comments/Corrections | |
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