Effect of high, medium, and low molecular weight hyaluronan on inflammation and oxidative stress in an in vitro model of human nasal epithelial cells

We investigated the pro or anti-inflammatory Hyaluronan (HA) activity at different molecular weights (MW) in an in vitro model of nasal inflammation IL-17A mediated. We evaluated the cytoplasmic ERK1/2 and IkBα phosphorylation,nuclear NF-kB signal pathway activation, ROS production, IL-8 and NOX-4 protein and mRNA levels, in nasal epithelial cells RPMI 2650 stimulated with recombinant human (rhIL-17A). The cells were treated with rhIL-17A in the presence or absence of HMW-HA (High-MW-HA; ∼1600 kDa), MMW-HA (Medium-MW-HA;∼900 kDa), LMW-HA (Low-MW-HA;500 kDa), and U0126 (specific inhibitor of MEK1and MEK2 MAP kinase kinase; MAPKK). We showed that rhIL-17A increased the ERK1/2, IkBα phosphorylation, NF-kB signal pathway activation, ROS production, IL-8 and NOX-4 proteins and mRNA levels. The addiction of HMW-HA or U0126, rather than MMW-HA or LMW-HA, showed a statistical significant down-regulatory effect on ERK1/2and IkBα phosphorylation, NF-kB signal pathway activation,ROS production, IL-8 and NOX-4 proteins in nasal epithelial cells stimulated with rhIL-17A. IL-17A might generate oxidative stress and inflammation via the activation ERK1/2/NFkB pathway in nasal epithelial cells. The HMW-HA might represent a coadjuvant of the classic anti-inflammatory/anti-oxidative treatment of nasal epithelial cells during IL-17A nasal inflammation.