Increased expression of YKL-40 in mild and moderate/severe persistent allergic rhinitis and its possible contribution to remodeling of nasal mucosa

Abstract

Background: Prominent expression of YKL-40 has been associated with pathological conditions characterized by tissue remodeling. We determined the expression level and distribution pattern of YKL-40 in allergic nasal mucosa and evaluated the effect of YKL-40 on the proliferation and migration of fibroblasts, the production of the mediators related to tissue remodeling, and collagen production. Additionally, the cytokine-driven regulation of YKL-40 expression was evaluated in cultured epithelial cells. Methods: The expression of YKL-40 in normal, mild, and moderate/severe allergic nasal mucosa was evaluated using real-time polymerase chain reaction (PCR), Western blot, and immunohistochemistry. Fibroblast migration was observed using a scratch wound method, and proliferation was determined by the MTT methods. Expression of proteoglycans, transforming growth factor (TGF) beta1, MMP2, MMP9, TIMP1, TIMP2, and collagen concentration were analyzed in fibroblasts treated with YKL-40. The expression levels of YKL-40 in cultured epithelial cells were examined after stimulation with mediators including Th2 cytokines, interferon (IFN) gamma, and TNF-alpha with real-time PCR and ELISA. Results: The expression of YKL-40 was up-regulated in allergic rhinitis and distributed in superficial epithelium, submucosal glands, and vascular endothelium, in addition to infiltrating cells. TGF-beta1, TIMP1, MMP9, and biglycan were up-regulated in fibroblasts on stimulation with YKL-40, accompanying increased proliferation and migration, and collagen production. IL-13, IFN-gamma, and TNF-alpha induced the increased production of YKL-40 in cultured epithelial cells. Conclusion: YKL-40 is up-regulated in mild and moderate/severe persistent allergic rhinitis, and its expression can be regulated differentially by different cytokines, possibly contributing to the remodeling of nasal mucosa in allergic rhinitis.