Higher Prostaglandin E2 Production by Dendritic Cells from Subjects with Asthma Compared with Normal Subjects
Julie A. Long,
Mirjana Fogel-Petrovic,
Darryl A. Knight,
Philip J. Thompson and
John W. Upham
Asthma and Allergy Research Institute, Sir Charles Gairdner Hospital; School of Medicine and Pharmacology, University of Western Australia; and Institute for Child Health Research, Perth, Western Australia, Australia
Correspondence and requests for reprints should be addressed to John Upham, M.B., B.S., F.R.A.C.P., Ph.D., Institute for Child Health Research, P.O. Box 855, West Perth, WA 6872, Australia. E-mail: johnu{at}ichr.uwa.edu.au
Dendritic cells (DCs) are thought to play an important rolein the pathogenesis of allergic disorders through their abilityto interact with T cells to initiate and amplify helper T cellType 2 immune responses. The mechanisms by which this occursare not completely understood, nor is it clear whether DC functiondiffers between normal individuals and individuals with asthma.We compared the function of DCs from 10 subjects with allergicasthma and 10 normal individuals, focusing on the productionof prostaglandin E (PGE) 2, interleukin (IL)-10, and IL-12 p70,mediators that play an important role in helper T cell Type1/Type 2 polarization. Monocyte-derived DCs were establishedby culturing monocytes with granulocyte-macrophage colony-stimulatingfactor and IL-4 for 7 days, and then stimulated with LPS plusIFN-. PGE2, IL-10, and IL-12 production was evaluated by ELISA,whereas cyclooxygenase-1, and -2 messenger RNA expression wasanalyzed using reverse transcription-polymerase chain reaction.LPS-stimulated monocyte-derived DCs from individuals with asthmaexhibited increased PGE2 and IL-10 production, but equivalentIL-12 p70 synthesis, when compared with DCs from normal subjects.Increased PGE2 synthesis by DCs from subjects with asthma wasassociated with an increase in cyclooxygenase-2 messenger RNAexpression. These findings support the notion that DC functionis significantly altered in allergic asthma.
A. Lundequist, S. N. Nallamshetty, W. Xing, C. Feng, T. M. Laidlaw, S. Uematsu, S. Akira, and J. A. Boyce Prostaglandin E2 Exerts Homeostatic Regulation of Pulmonary Vascular Remodeling in Allergic Airway Inflammation
J. Immunol.,
January 1, 2010;
184(1):
433 - 441.
[Abstract][Full Text][PDF]
T. H. Thatcher, R. P. Benson, R. P. Phipps, and P. J. Sime High-dose but not low-dose mainstream cigarette smoke suppresses allergic airway inflammation by inhibiting T cell function
Am J Physiol Lung Cell Mol Physiol,
September 1, 2008;
295(3):
L412 - L421.
[Abstract][Full Text][PDF]
K. F. Chung Evaluation of Selective Prostaglandin E2 (PGE2) Receptor Agonists as Therapeutic Agents for the Treatment of Asthma
Sci. Signal.,
September 27, 2005;
2005(303):
pe47 - pe47.
[Abstract][Full Text][PDF]
J. Shi, N. L. A. Misso, D. L. Duffy, B. Bradley, R. Beard, P. J. Thompson, and M-A. Kedda Cyclooxygenase-1 gene polymorphisms in patients with different asthma phenotypes and atopy
Eur. Respir. J.,
August 1, 2005;
26(2):
249 - 256.
[Abstract][Full Text][PDF]
L. Fabbri, S. P. Peters, I. Pavord, S. E. Wenzel, S. C. Lazarus, W. MacNee, F. Lemaire, and E. Abraham Allergic Rhinitis, Asthma, Airway Biology, and Chronic Obstructive Pulmonary Disease in AJRCCM in 2004
Am. J. Respir. Crit. Care Med.,
April 1, 2005;
171(7):
686 - 698.
[Full Text][PDF]