Document Detail

Cyclooxygenase-2 inhibits T helper cell type 9 differentiation during allergic lung inflammation via down-regulation of IL-17RB.
MedLine Citation:
PMID:  23449692     Owner:  NLM     Status:  MEDLINE    
RATIONALE: Helper CD4(+) T cell subsets, including IL-9- and IL-10-producing T helper cell type 9 (Th9) cells, exist under certain inflammatory conditions. Cyclooxygenase (COX)-1 and COX-2 play important roles in allergic lung inflammation and asthma. It is unknown whether COX-derived eicosanoids regulate Th9 cells during allergic lung inflammation.
OBJECTIVES: To determine the role of COX metabolites in regulating Th9 cell differentiation and function during allergic lung inflammation.
METHODS: COX-1(-/-), COX-2(-/-), and wild-type (WT) mice were studied in an in vivo model of ovalbumin-induced allergic inflammation and an in vitro model of Th9 differentiation using flow cytometry, cytokine assays, confocal microscopy, real-time PCR, and immunoblotting. In addition, the role of specific eicosanoids and their receptors was examined using synthetic prostaglandins (PGs), selective inhibitors, and siRNA knockdown.
MEASUREMENTS AND MAIN RESULTS: Experimental endpoints were not different between COX-1(-/-) and WT mice; however, the percentage of IL-9(+) CD4(+) T cells was increased in lung, bronchoalveolar lavage fluid, lymph nodes, and blood of allergic COX-2(-/-) mice relative to WT. Bronchoalveolar lavage fluid IL-9 and IL-10, serum IL-9, and lung IL-17RB levels were significantly increased in allergic COX-2(-/-) mice or in WT mice treated with COX-2 inhibitors. IL-9, IL-10, and IL-17RB expression in vivo was inhibited by PGD2 and PGE2, which also reduced Th9 cell differentiation of murine and human naive CD4(+) T cells in vitro. Inhibition of protein kinase A significantly increased Th9 cell differentiation of naive CD4(+) T cells isolated from WT mice in vitro.
CONCLUSIONS: COX-2-derived PGD2 and PGE2 regulate Th9 cell differentiation by suppressing IL-17RB expression via a protein kinase A-dependent mechanism.
Hong Li; Matthew L Edin; J Alyce Bradbury; Joan P Graves; Laura M DeGraff; Artiom Gruzdev; Jennifer Cheng; Ryan T Dackor; Ping Ming Wang; Carl D Bortner; Stavros Garantziotis; Anton M Jetten; Darryl C Zeldin
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Intramural    
Journal Detail:
Title:  American journal of respiratory and critical care medicine     Volume:  187     ISSN:  1535-4970     ISO Abbreviation:  Am. J. Respir. Crit. Care Med.     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-04-16     Completed Date:  2013-06-11     Revised Date:  2014-04-15    
Medline Journal Info:
Nlm Unique ID:  9421642     Medline TA:  Am J Respir Crit Care Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  812-22     Citation Subset:  AIM; IM    
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MeSH Terms
Asthma / immunology*
Cyclooxygenase 2 Inhibitors / immunology*
Cytokines / analysis
Eicosanoids / immunology,  physiology
Flow Cytometry
Inflammation / immunology
Lung / immunology*
Microscopy, Confocal
Models, Animal
Real-Time Polymerase Chain Reaction
Receptors, Interleukin-17 / immunology*
T-Lymphocyte Subsets / immunology*
Grant Support
Reg. No./Substance:
0/Cyclooxygenase 2 Inhibitors; 0/Cytokines; 0/Eicosanoids; 0/Il17rb protein, mouse; 0/Receptors, Interleukin-17
Comment In:
Am J Respir Crit Care Med. 2013 Apr 15;187(8):785-6   [PMID:  23586375 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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