Document Detail

Effects of leukotriene B4 and prostaglandin E2 on the differentiation of murine Foxp3+ T regulatory cells and Th17 cells.
MedLine Citation:
PMID:  19264469     Owner:  NLM     Status:  MEDLINE    
Leukotriene B4 (LTB4) and prostaglandin E2 (PGE2) are shown to be potent immunoregulatory lipid mediators. Here, we examined the effects of LTB4 and PGE2 on the differentiation of immunosuppressive CD4+CD25+Foxp3+ T regulatory cells (Treg) and pro-inflammatory IL-17-producing cells (Th17) from murine naïve CD4+ T cells. Using MACS-purified murine CD4+CD62L+ naïve T cells, we found that three days later in the presence of TGF-beta1, (28.65+/-6.83)% cells were converted into Treg cells, the mRNA expression of the key transcription factor Foxp3 peaked at 36h. Both LTB4 and PGE2 dose-dependently decreased the percentage of Treg cells and the mRNA expression of Foxp3. When the CD4+CD62L+ T cells were activated under Th17-promoting conditions in the presence of TGF-beta1 plus IL-6, three days later the production of IL-17 was markedly increased and the key transcription factor RORgammat mRNA peaked at 48h. LTB4 dose-dependently increased the secretion of IL-17 and the expression of RORgammat mRNA, whereas PGE2 decreased the secretion of IL-17 and the RORgammat mRNA expression. Our results suggest a distinct mode of immunoregulative action by PGE2 and LTB4, which may further our understanding of the role for lipid inflammatory mediators in the physiopathology of autoimmune diseases such as rheumatoid arthritis.
Haiying Chen; Jin Qin; Ping Wei; Jingge Zhang; Qiaoxia Li; Lihong Fu; Shujin Li; Chunling Ma; Bin Cong
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-03-04
Journal Detail:
Title:  Prostaglandins, leukotrienes, and essential fatty acids     Volume:  80     ISSN:  1532-2823     ISO Abbreviation:  Prostaglandins Leukot. Essent. Fatty Acids     Publication Date:  2009 Apr 
Date Detail:
Created Date:  2009-05-18     Completed Date:  2009-08-20     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  8802730     Medline TA:  Prostaglandins Leukot Essent Fatty Acids     Country:  Scotland    
Other Details:
Languages:  eng     Pagination:  195-200     Citation Subset:  IM    
Department of Forensic Medicine, Hebei Medical University, Shijiazhuang 050017, PR China.
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MeSH Terms
Cell Differentiation / drug effects*,  immunology
Dinoprostone / pharmacology*
Forkhead Transcription Factors / immunology
Immunologic Factors / pharmacology*
Interleukin-17 / immunology
Interleukin-6 / pharmacology
Leukotriene B4 / pharmacology*
Mice, Inbred C57BL
Nuclear Receptor Subfamily 1, Group F, Member 3
Receptors, Retinoic Acid / agonists,  antagonists & inhibitors,  immunology,  metabolism
Receptors, Thyroid Hormone / agonists,  antagonists & inhibitors,  immunology,  metabolism
T-Lymphocytes, Helper-Inducer / drug effects*,  immunology
T-Lymphocytes, Regulatory / drug effects*,  immunology
Transforming Growth Factor beta1 / pharmacology
Reg. No./Substance:
0/Forkhead Transcription Factors; 0/Foxp3 protein, mouse; 0/Immunologic Factors; 0/Interleukin-17; 0/Interleukin-6; 0/Nuclear Receptor Subfamily 1, Group F, Member 3; 0/Receptors, Retinoic Acid; 0/Receptors, Thyroid Hormone; 0/Rorc protein, mouse; 0/Transforming Growth Factor beta1; 363-24-6/Dinoprostone; 71160-24-2/Leukotriene B4

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