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Deficiency of cyclooxygenases transcripts in cultured primary bronchial epithelial cells of aspirin-sensitive asthmatics

100%

Pierzchalska M., Soja J., Wos M., Szabo Z., Nizankowska-Mogilnicka E., Sanak M., Szczeklik A.

Journal of Physiology and Pharmacology

2007

tom 58

nr 2

Background Airway function is actively regulated by epithelium through generating PGE2, the production of which depends on cyclooxygeneses (COX-1 and COX-2). Analysis of bronchial biopsies and bronchial epithelial cells in culture conducted so far gave conflicting results of expression pattern of these enzymes in healthy subjects and asthmatics patients, with and without aspirin hypersensitivity. Objective Our aim was to investigate the expression of COX-1 and COX-2 mRNA in primary human bronchial epithelial cells (HBEC) isolated from asthmatics and non-asthmatics. Methods We isolated HBEC from bronchial brushing preparations taken during bronchoscopy of 10 non-asthmatics (NA), 8 aspirin-tolerant asthmatics (ATA) and 9 aspirin-intolerant asthmatics (AIA). HBEC were cultured in serum free medium until 80% confluent. Total cellular RNA was isolated and reversed transcribed using oligo(dT)15 primers. Real time PCR was performed with primers to COX-1, COX-2, GAPDH and ß-actin in the presence of SYBR green dye. The cycle threshold (CT) for COX-1 or COX-2 was normalized using ß-actin and GAPDH as the internal standards. Results Not only COX-1 but also COX-2 mRNA were expressed by HBEC without any proinflammatory stimulation. We detected the smallest amount of COX-1 mRNA in the AIA group. The same trend was observed for COX-2 mRNA, though it didn’t reach the statistical significance. We also analysed the relationship between CTCOX-1 to CTCOX-2 by calculating the difference DCTCOX-1-COX-2. This analysis revealed that AIA group can be characterized by relatively smallest COX-1 mRNA expression in comparison to COX-2. There is a strong positive correlation between CTCOX1 and CTCOX2 in NA group (r=0.85; p< 0.001). In both groups of asthmatics this correlation is absent (ATA – r=0.5, p>0.1; AIA – r=0.43, p>0.1). Conclusions Cyclooxygeneases transcripts expression is altered in HBEC derived from the asthmatic patients, and this phenomenon is pronounced in case of aspirin hypersensitivity.

Effect of aspirin on cysteinyl leukotrienes production by eosinophils co-cultured with epithelial cells

100%

Jawien J., Olszanecki R., Lorkowska B., Korbut R.

Journal of Physiology and Pharmacology

2004

tom 55

nr 4

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 (PGE2) 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 PGE2 was decreased by aspirin (n=32). BEAS-2B cells barely formed Cys-LTs; addition of ASA increased this production, while production of PGE2 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.

Ograniczanie wyników

2 Journal of Physiology and Pharmacology

1 Jawien J.

1 Korbut R.

1 Lorkowska B.

1 Nizankowska-Mogilnicka E.

1 Olszanecki R.

1 Pierzchalska M.

1 Sanak M.

1 Soja J.

1 Szabo Z.

1 Szczeklik A.

1 Wos M.

1 2007

1 2004

Wyniki wyszukiwania

Deficiency of cyclooxygenases transcripts in cultured primary bronchial epithelial cells of aspirin-sensitive asthmatics

Effect of aspirin on cysteinyl leukotrienes production by eosinophils co-cultured with epithelial cells