Impact of CFTR ΔF508 mutation on prostaglandin E2production and type IIA phospholipase A2expression by pulmonary epithelial cells

Author:

Medjane Samir,Raymond Benoit,Wu Yongzheng,Touqui Lhousseine

Abstract

Cystic fibrosis (CF) is characterized by an exacerbated inflammatory pulmonary response with excessive production of inflammatory mediators. We investigated here the impact of cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction on prostaglandin E2(PGE2) production and type IIA secreted phospholipase A2(sPLA2-IIA) expression. We show that both resting and LPS-stimulated human respiratory epithelial cell line bearing ΔF508 mutation on CFTR (CF cells) released more PGE2than control cell line. This was accompanied by enhanced expression and activity of cyclooxygenase-2 in CF cells. PGE2release was attenuated after experimentally induced retrafficking of the ΔF508-CFTR at the plasma membrane. sPLA2-IIA expression occurred at higher levels in CF cells than in control cells and was enhanced by LPS and PGE2. Suppression of PGE2synthesis by aspirin led to an inhibition of LPS-induced sPLA2-IIA expression. Higher activation of NF-κB was observed in CF cells compared with control cells and was enhanced by LPS. However, addition of PGE2or aspirin had no effect on NF-κB activation. LPS-induced sPLA2-IIA expression was reduced by an NF-κB inhibitor. We suggest that the lack of the CFTR in the plasma membrane results in a PGE2overproduction and an enhanced sPLA2-IIA expression. This expression is upregulated by NF-κB and amplified by PGE2via a unidentified signaling pathway.

Publisher

American Physiological Society

Subject

Cell Biology,Physiology (medical),Pulmonary and Respiratory Medicine,Physiology

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