Club cell secretory protein 16 is a potential biomarker for silica-induced pulmonary fibrosis

CC16 and fibrosis

Abstract

This study was conducted to investigate the changes of Club cell protein 16 (CC16) and surfactant protein D (SP-D) levels in serum and bronchoalveolar lavage fluid (BALF) in silicotic rats and to explore their potential as early biomarkers for silicosis. Pulmonary fibrosis models of rats were constructed by exposing them to silica particles. BALF and serum were collected to determine CC16 and SP-D levels using enzyme-linked immunosorbent assay (ELISA) at different times after the exposure. Hydroxyproline (HYP) level in BALF and CC16 level in the lung tissues were also measured immunohistochemistrially. The BALF levels of CC16 decreased from 49.65 to 38.02 ng/mg after the rats were exposed to silica for 3 and 28 days, which were all significantly lower as compared with the controls (P<0.05), where the levels remained barely changed during the same period (61.27 to 56.76 ng/mg). The serum CC16 also showed a similar decrease from 9.8 ng/ml to 8.78 ng/ml during the period, while in the controls, the serum CC16 levels remained constantly between 11.04 and 10.96 ng/ml. The levels of SP-D in the serum of silica-exposed rats did not decrease as compared with the controls and BALF SP-D presented a parabolic curve change with silica exposure. Immunohistochemical examinations showed that the lung Club cells were severely damaged and CC16 expression was obviously decreased after silica exposure. BALF HYP level was higher in silica-exposed rats than in control only when the exposure was at 50 mg/ml. Our work demonstrates that expressions of CC16 and SP-D are pulmonary tissue-specific and CC16 expression is down-regulated as a result of silica-exposure. The significant relationship between CC16 and silica dose indicates that CC16 may be exploited as an early biomarker to assess silica-induced pulmonary fibrosis.