Increased phosphorylation of eNOS in nasal polyps of chronic rhinosinusitis patients can be diminished by 1,8-cineol.

INTRODUCTION

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a significant health problem, but the pathogenesis remains unclear to date. Nitric oxide (NO) has known airway modulating functions. Therefore, we investigated nitric oxide production to determine the role of eNOS in nasal polyps, with additional analysis of the effect of the monoterpene oxide 1,8-cineol on the possible regulation of eNOS signaling and thus NO production.

METHODS

We determined eNOS expression, as well as regulatory and effector proteins like NOSTRIN and CASP8, using whole genome microarray, immunohistochemistry and western blot. To evaluate the influence of 1,8-cineol on eNOS signaling, we examined tissue samples of nasal polyps of patients with CRSwNP incubated with 100 μM 1,8-cineol using quantitative real-time PCR, western blot and phosphorylation arrays.

RESULTS

Microarray analysis revealed an increased gene expression of eNOS (1.40-fold) as well as a decreased gene expression of NOSTRIN (0.53-fold) and CASP8 (0.44-fold) in nasal polyps. At the protein level, we detected 2.3-fold higher protein expression of eNOS and significant higher phosphorylation levels of eNOS in nasal polyps (19.7-fold, p ≤ 0.001) compared to inferior turbinates. Additionally, 1,8-cineol did not influence NOSTRIN and CASP8, but decreased the eNOS phosphorylation significantly (p ≤ 0.05).

DISCUSSION

Our study demonstrated for the first time that nasal polyps exhibit an increased phosphorylation of eNOS, which could be important for vascular permeability and the associated edema and elevated inflammation. Additionally, we detected that 1,8-cineol affects the eNOS phosphorylation significantly and thus its activation. This could be important to handle the elevated inflammation and edema formation by regulating the vascular permeability.