Vitamin D Decreases In Vitro Secretion of Matrix Metalloproteinase 2 and 9 from Nasal Polyp–Derived Fibroblasts

Abstract

Objectives:

In order to study the role of vitamin D in the pathogenesis and manifestation of chronic rhinosinusitis with nasal polyposis, we designed the following study. In vivo: We tried to determine if serum vitamin D level was lower in patients with chronic rhinosinusitis with nasal polyposis (CRSwNP) and if low serum vitamin D level correlated with the severity of CRSwNP. In vitro: We used the cultured nasal polyp–derived fibroblasts to investigate the in vitro effect of vitamin derivatives (calcitriol and tacalcitol) on the production of matrix metalloproteinase (MMP)-2 and MMP-9 .

Methods:

Patients with latest diagnosis of CRSwNP undergoing elective endoscopic sinus surgery were recruited, and patients with malignancies or asthma were excluded. The severity of CRSwNP was assessed with the Lund-Mackay score and polyp grading system. Vitamin D status was assessed by measuring circulating 25-hydroxyvitamin D (25OHD) by using commercial chemiluminescence immunoassay. Resected polyps were used for primary fibroblast culture. The fourth to eighth passage of human fibroblasts were used for the experiments.

Results:

Serum 25OHD levels (ng/mL ± SD) were significantly lower in patients with CRSwNP (21.4 ± 5.7) than in those with CRSsNP (28.8 ± 6.2) (P < .001). A significantly negative relationship was found between serum 25OHD level and polyp grade (r = –0.63, P = .001), indicating lower serum 25OHD was associated with higher polyp grade. Serum 25OHD was inversely related to both LM score and total IgE level as well. However, statistical significance was not found. In the in vitro study, we demonstrated that TNF can significantly induce the secretion of MMP-2 and-9 from nasal polyp fibroblasts and this effect was significantly suppressed by adding calcitriol and tacalcitol.

Conclusions:

A significantly lower vitamin D level was found in a group of Taiwanese CRSwNP patients, which revealed an association with greater nasal polyp size. The study on the influence of vitamin D on inflammatory processes in NP may shed a light not only on the mechanism of its etiology but also prove its potential use in the pharmacology of NP.