Relationship of TLR2, TLR4 and tissue remodeling in chronic rhinosinusitis

In order to explore the role of innate immunity in the remodeling of CRS (chronic rhinosinusitis), we investigated the correlation between TLR2, TLR4 and remodeling involved cytokines and histopathological features. Immunohistochemical staining was applied to detect the expression of TLR2, TLR4 and TGF-β1. Masson staining was used for observing the collagen deposition. The other histopathologic features of remodeling were observed by hemotoxylin and eosin (HE) staining. Nasal epithelial cell culture was used to elucidate the effect of TLR2, TLR4 agonists and inhibitors on the expression of TGF-β1 and MMP-9. The association study showed that the significantly higher expression of TLR2, TLR4, TGF-β1 and collagen appeared in CRSsNP (chronic rhinosinusitis without nasal polyps) patients compared with CRSwNP (chronic rhinosinusitis with nasal polyps) patients. In CRSsNP, patients with a severe epithelial damage (score 3) had a significantly higher expression of TLR2 than patients with mild epithelial damage (score ≤ 2) (P < 0.05). Moreover the expression of TLR2 correlated negatively with squamous hyperplasia in CRSsNP, and positively with gland hyperplasia in CRSwNP. The expression of TLR2 and TLR4 was closely related to neutrophil infiltration in CRSsNP (P < 0.01). TGF-β1 was downregulated by TLR2 agonist in CRSwNP and upregulated by TLR4 agonist in CRSsNP (P < 0.05). MMP-9 was upregulated by TLR4 agonist in CRSwNP (P < 0.05). TLR2 and TLR4 had close relationship with TGF-β1 and the histologic features of remodeling, especially collagen deposition and neutrophil infiltration in CRSsNP. The innate immunity could influence the histologic characteristics and involved cytokines through TLR2 and TLR4 in the remodeling of CRS.