Effect of aspirin on cysteinyl leukotrienes production by eosinophils co-cultured with epithelial cells.
Eosinophils have long been considered to play solely crucial role in the pathogenesis of aspirin-induced asthma, however increasing evidence suggest that the bronchial epithelium is also involved in the initiation and maintenance of allergic inflammation. Epithelial cells and eosinophils retained within airways interact reciprocally to mount and sustain inflammatory response. Recently, we have shown that eosinophil-epithelial cell interactions are capable of amplifying the production of cysteinyl leukotrienes (Cys-LTs). The aim of this study was to investigate if there is any influence of aspirin (ASA) on Cys-LTs and prostaglandin E2 (PGE(2)) production in the model of co-cultured human epithelial cells (line BEAS-2B) and human eosinophils. Synthesis of Cys-LTs in eosinophils was increased after incubation with ASA. At the same time the production of PGE(2) was decreased by aspirin (n=32). BEAS-2B cells barely formed Cys-LTs; addition of ASA increased this production, while production of PGE(2) was inhibited by aspirin (n=32). Synthesis of Cys-LTs by eosinophils co-incubated with BEAS-2B was nearly 7-fold higher than that of activated eosinophils alone (1631.5 pg/ml +/- 154 vs. 258 pg/ml +/- 31; p<0.05; n=32). Surprisingly, in the eosinophil-epithelial cell co-culture, aspirin inhibited both augmentation of Cys-LTs synthesis (from 1631.5 pg/ml +/- 154 to 1458 pg/ml +/- 137; p<0.05; n=32) and the production of PGE2 (from 2640 pg/ml +/- 231 to 319 pg/ml +/- 27; p<0.05; n=32). In summary, we have demonstrated that interactions between non-atopic eosinophils and epithelial cells result in augmentation of Cys-LTs production, and this augmentation could be inhibited by aspirin.
Jawień
J
J
Pharmacology, Jagiellonian University School of Medicine, Grzegorzecka Str. 16, 31-531 Krakow, Poland. mmjawien@cyf-kr.edu.pl
Olszanecki
R
R
Lorkowska
B
B
Korbut
R
R
D001241:Aspirin / Q000494:pharmacology*; D018920:Coculture Techniques / Q000379:methods; D004804:Eosinophils / Q000187:drug effects* / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D015289:Leukotrienes / Q000096:biosynthesis*; D008565:Membrane Proteins / Q000096:biosynthesis; D018077:Receptors, Leukotriene / Q000096:biosynthesis
D015289:Leukotrienes; D008565:Membrane Proteins; D018077:Receptors, Leukotriene; C083169:leukotriene D4 receptor; D001241:Aspirin