Abstract
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-17A mediated. We evaluated the ERK1/2 and IκBα phosphorylation, NF-κB 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. Furthermore, the cells were treated with HMW-HA, MMW-HA, LMW-HA, and U0126. Our results showed that rhIL-17A increased the ERK1/2, IκBα phosphorylation and NF-κB signal pathway activation, ROS production, IL-8 and NOX-4 proteins, and mRNA levels. The addiction of HMW-HA or U0126 showed a significant downregulatory effect on inflammation due to the rhIL-17A stimulation in nasal epithelial cells. IL-17A is able to generate oxidative stress and inflammation via the activation of ERK1/2/NF-κB pathway in nasal epithelial cells. The HMW-HA might represent a coadjuvant of the classic anti-inflammatory/antioxidative treatment of nasal epithelial cells during IL-17A nasal inflammation.
Highlights
Allergic rhinitis is an extremely common medical problem characterized by nasal congestion, clear rhinorrhea, sneezing, and itching
The levels of pERK1/ 2/total ERK1/2 ratio and pNF-κB/total Nuclear factor- (NF-)κB ratio significantly increased in the cells stimulated with rhIL-17A (p < 0.002 and p < 0.0001, resp.) and showed a statistically significant decrease when the cells were preincubated with U0126 (p < 0.003 and p < 0.002 resp.) (Figure 1(b))
The pretreatment of the RPMI 2650 with high molecular weight polymer (HMW)-HA significantly inhibited the levels of pERK1/2 (p < 0.0001) and pIκBα (p < 0.0001) in the cells stimulated with rhIL-17A, compared to the cells treated with rhIL-17A alone (Figure 3(a))
Summary
Allergic rhinitis is an extremely common medical problem characterized by nasal congestion, clear rhinorrhea, sneezing, and itching. The presence of an uncontrolled inflammation in the upper airways may compromise the control of allergic rhinitis with a consequent progression of the diseases [1]. IL-17A and oxidative stress are involved in the development and progression of allergic rhinitis by the activation of nasal epithelial cells [2]. Hyaluronan (HA) is a glycosaminoglycan widely distributed in tissues and is a normal constituent of airway secretions [3, 4]. It is a major component of the extracellular matrix and it plays a key role in regulating inflammation that is associated with accumulation and turnover of HA polymers by multiple cell types. Through the years, HA has become recognized as an active participant in inflammatory, angiogenic, fibrotic, and cancer promoting processes [5]
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