Implication of NADPH oxidases in the early inflammation process generated by cystic fibrosis cells.
In cystic fibrosis (CF) patients, pulmonary inflammation is a major cause of morbidity and mortality. The aim of this study was to further investigate whether oxidative stress could be involved in the early inflammatory process associated with CF pathogenesis. We used a model of CFTR defective epithelial cell line (IB3-1) and its reconstituted CFTR control (S9) cell line cultured in various ionic conditions. This study showed that IB3-1 and S9 cells expressed the NADPH oxidases (NOXs) DUOX1/2 and NOX2 at the same level. Nevertheless, several parameters participating in oxidative stress (increased ROS production and apoptosis, decreased total thiol content) were observed in IB3-1 cells cultured in hypertonic environment as compared to S9 cells and were inhibited by diphenyleneiodonium (DPI), a well-known inhibitor of NOXs; besides, increased production of the proinflammatory cytokines IL-6 and IL-8 by IB3-1 cells was also inhibited by DPI as compared to S9 cells. Furthermore, calcium ionophore (A23187), which upregulates DUOX and NOX2 activities, strongly induced oxidative stress and IL-8 and IL-6 overexpression in IB3-1 cells. All these events were suppressed by DPI, supporting the involvement of NOXs in the oxidative stress, which can upregulate proinflammatory cytokine production by the airway CFTR-deficient cells and trigger early pulmonary inflammation in CF patients.
INSERM U-773, Centre de Recherche Biomédicale Bichat, Beaujon (CRB3), Faculté de Médecine Xavier Bichat, Université Paris Diderot Paris 7, 75018 Paris, France ; Département de Biochimie, UFR des Sciences Pharmaceutiques et Biologiques, Université Paris Descartes, Sorbonne Paris Cité, 75006 Paris, France.
Nushjira
N
Pongnimitprasert
Margarita
M
Hurtado
Foudil
F
Lamari
Jamel
J
El Benna
Corinne
C
Dupuy
Michèle
M
Fay
Marie-José
MJ
Foglietti
Maguy
M
Bernard
Marie-Anne
MA
Gougerot-Pocidalo
Françoise
F
Braut-Boucher