Exocrine cell-derived microparticles in response to lipppolysaccharide promote endocrine dysfunction in cystic fibrosis - Université de Bourgogne Accéder directement au contenu
Article Dans Une Revue Journal of Cystic Fibrosis Année : 2014

Exocrine cell-derived microparticles in response to lipppolysaccharide promote endocrine dysfunction in cystic fibrosis

Résumé

Background Diabetes in cystic fibrosis (CF) is a result of exocrine pancreas alteration followed by endocrine dysfunction at a later stage. Microparticles (MPs) are plasma membrane fragments shed from stimulated or damaged cells that act as cellular effectors. Our aim was to identify a new form of interaction between exocrine and endocrine pancreatic cells mediated by exocrine MPs, in the context of recurrent infection in CF. Methods MPs from either human exocrine CFTRΔF508-mutated (CFPAC-1) cells or exocrine normal pancreatic (PANC-1) cells were collected after treatment by LPS from Pseudomonas aeruginosa and applied to rat endocrine normal insulin-secreting RIN-m5F cells. MP membrane integration in target cells was established by confocal microscopy and flow cytometry using PKH26 lipid probe. Apoptosis, lysosomal activity, insulin secretion were measured after 18 h. MP-mediated NF-κB activation was measured in HEK-Blue reporter cells by SEAP reporter gene system and in RIN-m5F cells by Western blot. In endocrine normal cells, CFTR inhibition was achieved using Inhibitor-172. Results Compared to PANC-1, MPs from CFPAC-1 significantly reduced insulin secretion and lysosomal activity in RIN-m5F. MPs induced NF-κB activation by increasing the level of IκB phosphorylation. Moreover, the inhibition of NF-κB activation using specific inhibitors was associated with a restored insulin secretion. Interestingly, CFTR inhibition in normal RIN-m5F cells promoted apoptosis and decreased insulin secretion. Conclusions During recurrent infections associated with CF, exocrine MPs may contribute to endocrine cell dysfunction via NF-κB pathways. Membrane CFTR dysfunction is associated with decreased insulin secretion.

Dates et versions

hal-00966558 , version 1 (26-03-2014)

Licence

Paternité - Pas d'utilisation commerciale

Identifiants

Citer

Andrei Alexandru Constantinescu, Céline Gleizes, Mahmoud Alhosin, Elhassan Yala, Fatiha Zobairi, et al.. Exocrine cell-derived microparticles in response to lipppolysaccharide promote endocrine dysfunction in cystic fibrosis. Journal of Cystic Fibrosis, 2014, 13, pp.219-226. ⟨10.1016/j.jcf.2013.08.012⟩. ⟨hal-00966558⟩
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