Functional Evaluation of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) in human monocytes (original) (raw)

2009, Journal of Cystic Fibrosis

NP is a useful model to study pathogenesis of chronic airway inflammation. NP could be either of unknown origin (primary NP) or secondary to congenital impairment of mucociliary clearance (CF, or primary ciliary dyskinesia, PCD). The aim of the present study was to identify the differentially expressed proteins using human nasal epithelial cell (HNEC) primary cultures from NP, and two successive proteomic approaches (2D gels following mass spectrometry (MS) and semi-quantitative iTRAQ MS/MS analysis). Using 2D approach, 51 proteins were identified (pH range 5−8) with 7 being differentially expressed between primary NP (n = 4) and secondary NP (2 CF, 2 PCD). Using iTRAQ approach, 583 proteins were identified with 21 and 25 of them being differentially expressed between primary NP (n = 1) vs control mucosa (n = 1) and primary NP (n = 1) vs CF NP (n = 1), respectively. These proteins include inflammatory (annexin 1 and 2), oxidative stress (peroxiredoxin 1, GSTp1), structural (keratin 18, alpha actinin) and chaperone proteins (several HSPs). Multiple proteins belonging to Unfolding Protein Response (UPR) proteins (e.g. PPIB, HSP70, GRP78) were also identified. Focusing on the UPR, we found that UPR decreases as function of time in HNEC cultures from p_NP (n = 3). Cytokine secretion, measured in same HNEC, decreases in parallel to UPR response (n = 3). All together, these results suggest that UPR is related to inflammatory microenvironment and play a role in pathogenesis of primary and CF NP.