Effect of phosphodiesterase IV inhibitors on eotaxin expression in bronchial epithelial cells – Comparison between immortalized and primary line

Eotaxins are an important agents of the patophysiology in the obstructive airway diseases. They are responsible for eosinophil recrutation into respiratory tract. Phosphodiesterases (PDEs) are a huge and diversified family of enzymes decomposing cAMP. PDE4 inhibitors as drugs, act through cAMP elevation and can inhibit inflammation in many ways. The aim of this work was to evaluate the effect of PDE4 inhibitors (rolipram and RO-20-1724) on eotaxin (CCL11, CCL24 and CCL26) expression in human bronchial epithelial cells: immortalized - BEAS-2B (ATCC) and primary (ATCC). Cells were preincubated with PDE4 inhibitors for 1 h and stimulated with IL-4+TNF-α or IL-13+TNF-α for 48h. Protein levels were measured using ELISA kits, changes in genes expression were measured using real time PCR. Results: The both of cell lines produced different eotaxins: BEAS-2B synthesized CCL11 and CCL26, PBEC - CCL24 and CCL26. Distinct effects of PDE4 inhibitors in immortalized as compared to primary cell line were observed. PDE4 inhibitors decreased the mean level of eotaxin gene and protein expression in BEAS-2B usually in statistically significant manner. PDE4 inhibitors stimulated eotaxin gene expression; specially rolipram significantly increased the mean levels of eotaxin gene expression, but did not change their protein synthesis. Conclusions: Our results do not permit to predict the effects of PDE4 inhibitors on bronchial epithelial cells because of the differences in the biology of the both used cell lines. Unequivocal resolution of the problem needs more experimental trials using more primary cell lines or experimental animal model.