Effect of High, Medium and Low molecular weight hyaluronan on inflammation and oxidative stress in an in vitro model of Human Nasal Epithelial cells

IL-17A is involved in the activation of oxidative stress and inflammation in nasal epithelial cells. Hyaluronan (HA) in its high molecular weight form (HMW-HA) shows anti inflammatory responses in contrast to low and medium molecular weight HA (LMW-HA and MMW-HA). The aim of this study was to investigate the pro- or anti-inflammatory biologic function of HA at different molecular weight in an in vitro model of nasal inflammation IL-17 mediated. We evaluated the ERK1/2 and I?B?phosphorylation, NF-?B signal pathway activation, ROS production, IL-8 and NOX-4 protein, and mRNA levels, in nasal epithelial cells RPMI 2650 stimulated with recombinant human (rh) IL-17A or PMA. Furthermore, the cells were treated with HMW-HA, MMW-HA, LMW-HA and U0126 (specific inhibitor of MEK1and MEK2 MAP kinase kinase). To confirm the specific action of HA, HMW-HA samples were degraded with Streptomyces hyaluronidase. Our results showed that rhIL-17A increased the ERK1/2, I?B? phosphorylation and NF-?B signal pathway activation, ROS production, IL-8 protein and mRNA levels, NOX-4 protein but not mRNA transcript. The addiction of HMW-HA or U0126 showed a significant downregulatory effect on inflammation due to the rhIL-17A stimulation in nasal epithelial cells. HMW-HA is able to downregulate the mechanism of uncontrolled oxidative stress and inflammation typical of upper airway diseases. Indeed, our results provided encouraging evidence to support possible beneficial effects of HMW-HA in the care of patients with altered function of nasal epithelial cells, supporting its potential ancillary role as coadjuvant of the classic anti-inflammatory treatment of the nose.