Higher prostaglandin e2 production by dendritic cells from subjects with asthma compared with normal subjects

Dendritic cells (DCs) 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 helper T cell Type 2 immune responses. The mechanisms by which this occurs are not completely understood, nor is it clear whether DC function differs between normal individuals and individuals with asthma. We compared the function of DCs from 10 subjects with allergic asthma and 10 normal individuals, focusing on the production of prostaglandin E (PGE) 2, interleukin (IL)-10, and IL-12 p70, mediators that play an important role in helper T cell Type 1/Type 2 polarization. Monocyte-derived DCs were established by culturing monocytes with granulocyte-macrophage colony-stimulating factor and IL-4 for 7 days, and then stimulated with LPS plus IFN-gamma. PGE2, IL-10, and IL-12 production was evaluated by ELISA, whereas cyclooxygenase-1, and -2 messenger RNA expression was analyzed using reverse transcription-polymerase chain reaction. LPS-stimulated monocyte-derived DCs from individuals with asthma exhibited increased PGE2 and IL-10 production, but equivalent IL-12 p70 synthesis, when compared with DCs from normal subjects. Increased PGE2 synthesis by DCs from subjects with asthma was associated with an increase in cyclooxygenase-2 messenger RNA expression. These findings support the notion that DC function is significantly altered in allergic asthma.