Nebulized Hyaluronan Ameliorates lung inflammation in cystic fibrosis mice

• DOI: 10.1002/ppul.22637
• Publication Date: 2012-07-23T12:23:21Z
• Authors: Manuela Gavina; Alessandro Luciani; Valeria R. Villella; Speranza Esposito; Eleonora Ferrari; Ilaria Bressani; Alida Casale; Emanuela M. Bruscia; Luigi Maiuri; Valeria Raia
• Keywords: 0301 basic medicine; Cystic Fibrosis; Nebulizers and Vaporizers; 610; Pneumonia; Respiratory Mucosa; 3. Good health; Cell Line; Disease Models, Animal; Mice; 03 medical and health sciences; Treatment Outcome; Adjuvants, Immunologic; Administration, Inhalation; Animals; Humans; Mice, Inbred CFTR; Female; Hyaluronic Acid; Reactive Oxygen Species

Abstract Rationale Chronic lung inflammation with increased susceptibility to bacterial infections cause much of the morbidity and mortality in patients cystic fibrosis (CF), most common severe, autosomal recessively inherited disease Caucasian population. Exogenous inhaled hyaluronan (HA) can exert a protective effect against injury beneficial effects HA have been shown experimental models chronic respiratory diseases. Our objective was examine whether exogenous administration nebulized might interfere CF. Study design/methods F508del homozygous mice ( Cftr ) transgenic overexpressing ENaC channel β‐subunit (Scnn1b‐Tg) were treated (0.5 mg/mouse/day for 7 days). Tumor necrosis factor‐alpha (TNFα), macrophage inflammatory protein‐2 (MIP‐2), myeloperoxidase (MPO) levels, infiltration assessed on tissues. IB3‐1 CFBE41o‐epithelial cell lines cultured (24 hr, 100 µg/ml) Reactive Oxygen Species (ROS), Tissue Transglutaminase (TG2) SUMOylation Peroxisome Proliferator Activated Receptor gamma (PPARγ) phospho‐p42/p44 levels measured by dichlorodihydrofluorescein assay, or fluorescence resonance energy transfer (FRET) microscopy immunoblots. Results Nebulized reduced TNFα expression P < 0.005); TNFα, MIP‐2, MPO protein 0.05); activity CD68+ cells counts 0.005) tissues Scnn1b‐Tg mice, compared saline‐treated mice. ROS, TG2 SUMOylation, activity, phospho‐p42‐44, PPARγ both CFBE41o 0.05). Conclusions is effective controlling vivo CF airways vitro human airway epithelial cells. We provide proof concept use as potential anti‐inflammatory drug therapy. Pediatr Pulmonol. 2013; 48:761–771. © 2012 Wiley Periodicals, Inc.