Effect of cigarette smoke on human respiratory culture epithelium: expression and activity of CFTR, oxidative stress and inflammatory response.

CLAUZURE, MARIÁNGELES; ; DUGOUR, ANDREA V.;; SANTA-COLOMA, T.A.; VALDIVIESO, ÁNGEL G.;; FIGUEROA, JUAN M.;

Mar del Plata

Congreso; . LXI Reunión de la Sociedad Argentina de Investigación Clínica (SAIC). Noviembre 16-19, 2016; 2016

The chronic obstructive pulmonary disease C12& is directlyrelated to cigarette consumption. Recent evidences suggest apossible relationship betYeen the CFT4 Cl- channel and C12&CFT4 mutations cause cystic fibrosis CF. $oth disorders shareclinical and functional similarities, in particular oxidative stressand inflammation. +n CF cells, a CFT4 failure is also associatedYith a mitochondrial complex + mCx+ dysfunction. Here Yeinitiated studies on the mechanism involved in the inflammatoryresponse in C12&, and the possible role of CFT4. Calu cellshuman lung epithelium Yere treated Yith a concentrated extractof smoMe CSE for h and the CFT4 activity using S23and expression q4T2C4, the production of reactive oxygenspecies 41S &CFH&A for total 41S and /itoS1:? formitochondrial 41S, the mCx+ activity measuring mitochondrial0A&Hcytochrome c reductase activity and the release of +Lby Elisa Yere measured. CSE treatment significantly decreasedthe CFT4 expression and activity. This Yas accompanied by asignificant decrease of the mCx+ activity and a significant increasein 41S levels, in concordance Yith the increased release of +L.The addition of 0AC together Yith CSE prevented the increased41S and +L levels, but did not prevented the decreased CFT4 expression nor the mCx+ dysfunction. Also, treatment Yith the0FM$ inhibitor +-- abolished the increased +L secretion. Theresults suggest that CSE effects on +L are mediated througha 41Sinduced activation of 0FM$. CSE is also able to causechanges in CFT4, mCx+ and 41S similar to those observedin CF cells. The understanding of the mechanisms involved inthese effects Yould be of interest for the development of neYtherapeutic strategies. AcMnoYledgements Supported by grants2+CT and 2+CT from A02C;T to TASC2+2 and 2+2 to TASC C10+CET 7CA to TASC and Fundación Cassaráto FJM and DAV.