Published ahead of print on May 19, 2004, doi:10.1164/rccm.200311-1595OC Am. J. Respir. Crit. Care Med., Volume 170, Number 5, September 2004, 485-491 A more recent version of this article appeared on September 1, 2004
Submitted on November 25, 2003 Higher Prostaglandin E2 Production by Dendritic Cells From Asthmatics Compared to Normal SubjectsJulie A Long1,1 Asthma and Allergy Research Institute, Sir Charles Gairdner Hospital, Perth, WA, Australia; School of Medicine and Pharmacology, University of Western Australia, Perth, WA, Australia, 2 School of Medicine and Pharmacology, University of Western Australia, Perth, WA, Australia; Asthma and Allergy Research Institute, Sir Charles Gairdner Hospital, Perth, WA, Australia * To whom correspondence should be addressed. E-mail: johnu{at}ichr.uwa.edu.au.
Dendritic cells (DC) are thought to play an important role in the pathogenesis of allergic disorders through their ability to interact with T-cells to initiate and amplify Th2 immune responses. The mechanisms by which this occurs are not completely understood, nor is it clear whether DC function differs between normal individuals and asthmatics. We compared the function of DC from 10 allergic asthmatic and 10 normal individuals, focusing on the production of prostaglandin (PG) E2, IL-10 and IL-12p70, mediators that play an important role in Th1/Th2 polarization. Monocyte-derived DC (Mo-DC) were established by culturing monocytes with GM-CSF and IL-4 for 7 days, and then stimulated with lipopolysaccharide (LPS) + interferon (IFN) Key words: asthma, dendritic cells, PGE2, cyclo-oxygenase, IL-10
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. PGE2, IL-10 and IL-12 production was evaluated by ELISA, while cyclooxygenase (COX) -1, and -2 mRNA expression were analyzed using RT-PCR. LPS stimulated Mo-DC from asthmatic individuals exhibited increased PGE2 and IL-10 production, but equivalent IL-12 p70 synthesis, when compared with DC from normal subjects. Increased PGE2 synthesis by asthmatic DC was associated with an increase in COX-2 mRNA expression. These findings support the notion that DC function is significantly altered in allergic asthma.
