A correlative study of NF-κB activity and cytokines expression in human chronic nasal sinusitis

Abstract

A growing body of literature suggests that cytokines play an important part in the pathogenesis of chronic nasal sinusitis. However, the mechanism by which the expression of cytokines in chronic nasal sinusitis is upregulated has not been well documented. The present study investigated the role of nuclear factor-kappa B (NF-κB) activation in upregulating the expression of interleukin-5, -6 and -8 (IL-5, IL-6 and IL-8). We titrated the levels of IL-5, IL-6 and IL-8 in nasal mucosa in 52 cases of chronic nasal sinusitis and 12 normal subjects using enzyme-linked immunosorbent assay. According to whether allergic rhinitis was associated or not, we subdivided the patients into the AR group (with allergic rhinitis) and the NAR group (without allergic rhinitis). Semi-quantitative reverse transcription-polymerase chain reaction and immunohistochemical staining were used to evaluate expression and activation of NF-κB P50 and P65 subunits in nasal mucosa. The correlation between activities of P50 and P65 and cytokines expression was analysed. Our results showed that IL-5, IL-6 and IL-8 in both the AR and NAR groups were strikingly elevated in comparison with the control group (all p < 0.01 for AR group; p < 0.05, 0.05, 0.01, respectively, for NAR group); and they were even higher in the AR group than those in the NAR group (p < 0.01, 0.05, 0.01, respectively). P50 and P65 mRNA levels in both AR and NAR groups were markedly greater than those in the control group (all p < 0.01); and the AR group had further higher levels as compared with the NAR group (both p < 0.05). Immunohistochemical study revealed that nucleus-positive rates of P50 and P65 in both AR and NAR groups were significantly higher than those of the control group (all p < 0.01), and they were much greater in the AR group in comparison with the NAR group (all p < 0.01). Pearson correlation analysis demonstrated that P50 and P65 nucleus-positive rates were closely correlated with IL-6 and IL-8 levels, but not IL-5, with a correlation coefficient of 0.49 for P50 and IL-6, 0.54 for P50 and IL-8, 0.61 for P65 and IL-6, and 0.66 for P65 and IL-8 (all p < 0.01). In conclusion, upregulated expression and activation of NF-κB P50 and P65 might be one of the mechanisms for induction of IL-6 and IL-8 expression in chronic nasal sinusitis. Association of allergic rhinitis with chronic nasal sinusitis further enhanced NF-κB activity, and subsequently lead to even stronger expression of IL-6 and IL-8. IL-5 expression appeared to be independent of NF-κB pathway in chronic nasal sinusitis.