Flagellin/Toll-like Receptor 5 Induces Interleukin-17C in Human Nasal Epithelia

Abstract

Objectives:

Recently, it has been reported that IL-17C mediates innate immune responses against microbial infection and inflammation in mucosal epithelium. However, little is known about the expression and biological function of IL-17C in human airway epithelium.

Methods:

The family of Interleukin-17 (IL-17) cytokine is involved in host defense responses and various inflammatory diseases. Many studies indicate that IL-17A and IL-17F play an important role in the pathogenesis of airway inflammatory diseases. In this study, we found that IL-17C mRNA expression was strongly induced by inflammatory cytokines such as TNF-α or IL-1β and bacterial flagellin, recognized by toll-like receptor 5 (TLR5), in primary cultured normal human nasal epithelial (NHNE) cells. We also confirmed that IL-17C protein production was enhanced by TNF-α, IL-1β and flagellin.

Results:

We demonstrated that pretreatment of neutralizing antibody against TLR5 completely inhibited flagellin-induced IL-17C expression, indicating elevated IL-17C expression is specifically mediated by flagellin/TLR5 engagement. Moreover, IL-17C stimulation induced innate immune responses including the expression of antibacterial peptides and proinflammatory cytokines in NHNE cells. Taken together, these results show that IL-17C expression is enhanced in response to inflammation and flagellin/TLR5 activation and involved in inflammatory process in human nasal epithelial cells.

Conclusions:

Our findings suggest that IL-17C cytokine may play an important role in TLR5-dependent innate immune responses of human airway epithelia.