Effect of Caffeic Acid on Nasal Polyp Derived Fibroblasts

Abstract

Objectives: Caffeic acids are known to have anti-oxidant, anti-inflammatory, immunomodulatory, and tissue reparative effects. The purposes of this study were to determine the effect of caffeic acid on transforming growth factor (TGF)-β1-induced myofibroblast differentiation and collagen production, and to determine whether caffeic acid is involved in the antioxidant effect. Method: Nasal polyp-derived fibroblasts (NPDFs) were pre-treated with caffeic acid (5-25 µM) for 2 hours and stimulated with TGF-β1 (5 ng/mL) for 24 hours. The expression of α-SMA, collagen types I and III, and Nox4 mRNA was determined by a reverse transcription-polymerase chain reaction, and the expression of α-SMA protein was determined by immunofluorescence microscopy. The amount of total soluble collagen production was analyzed by the Sircol collagen dye-binding assay. The reactive oxygen species (ROS) generated by NPDFs were determined using 2′,7′-dichlorfluorescein-diacetate. siNox4 was used to determine the effect of Nox4. Results: The expression of α-SMA and production of collagen were significantly increased following TGF-β1 treatment. In contrast, the level of expression of α-SMA and the level of production of collagen were decreased by pre-treatment with caffeic acid. The activation of Nox4 and the subsequent production of ROS were also reduced by pre-treatment with caffeic acid. The expression of α-SMA was prevented by inhibition of ROS generation with siNox4. Conclusion: Caffeic acid may inhibit TGF-β1-induced differentiation of fibroblasts into myofibroblasts and collagen production by regulating NADPH oxidase-derived ROS.