Inhibition of p38 mitogen activated protein kinase controls airway inflammation in cystic fibrosis

SUMOylation of Tissue Transglutaminase as Link between Oxidative Stress and Inflammation

“…We have already validated this experimental model (22,41) and reported that increased TG2 levels are a feature of CF nasal polyp mucosa and that the inhibition of TG2 is effective in controlling mucosal inflammation by restoring normal levels of PPAR␥ protein (22). We found that TG2-PIASy colocalized in human CF airways (Fig.…”

“…The inflammatory response is a complex event involving different cell types interacting within their natural environment. We took advantage of a well-established model of in vitro cultures of explants of CF nasal polyps, which are routinely removed surgically and represent CF chronic airway inflammation (22,41). We demonstrated that ROS-mediated PIASy-TG2 as well as SUMO-1-TG2 interactions take place in human CF airways.…”

“…To investigate whether TG2-PIASy interaction and TG2 SUMOylation may take place in human airways of CF patients and whether it was induced by the oxidative stress, we used a wellestablished tissue culture model of biopsies of human CF nasal polyps (22,41). We have already validated this experimental model (22,41) and reported that increased TG2 levels are a feature of CF nasal polyp mucosa and that the inhibition of TG2 is effective in controlling mucosal inflammation by restoring normal levels of PPAR␥ protein (22).…”

Targeting autophagy as a novel strategy for facilitating the therapeutic action of potentiators on ΔF508 cystic fibrosis transmembrane conductance regulator

“…To translate these findings to human CF airways, we used an ex-vivo model of cultured nasal polyp biopsies belonging to CF patients, a useful tool to test potential strategies of modulation of mucosal response to environmental triggers within their natural environment. 7,24,25,49 Nasal polyp biopsies from five ΔF508/ΔF508 patients ( Table 1A, Patients #1-5) were treated with cystamine for 18 h, washed and then cultured for further 36 h in the absence of cystamine. The cystamine-mediated rescue of CFTR at the epithelial surface persisted for 36 h after cystamine withdrawal and was abrogated by 3-MA ( Fig.…”

“…Nasal polyp biopsies from 5 ΔF508 homozygous patients undergoing surgical treatment for nonallergic nasal polyposis (see Table 1A) were cultured as previously described, 7,24,25,49 for 18 h with medium, cystamine (250 μM) or EUK-134 (50 μg ml -1 , Vinci Biochem, 10006329), followed by 36 h of incubation with medium alone in presence or absence of 3-MA, and then pulsed for 30 min with medium or genistein followed by 4 h of PA-LPS challenge.…”