Melamine activates NFκB/COX-2/PGE2 pathway and increases NADPH oxidase-dependent ROS production in macrophages and human embryonic kidney cells.

Melamine is a wildly used compound in manufactures of plastics and resins. A variety of toxic effects from melamine, including nephrolithiasis, chronic kidney inflammation, and bladder carcinoma, have been mentioned. Oxidative stress is considered to be an important pathogenic mechanism of kidney disease which may develop from an increasing free radical production through inflammation. The aim of this study is to investigate melamine-induced oxidative stress and inflammation in macrophage-like cell line RAW 264.7 and human embryonic kidney cell line HEK293. Results indicated melamine activated nuclear factor (NF)-κB through increasing IκB-α degradation and NF-κB p65/p50 DNA-binding activity. In addition, melamine significantly increased COX-2 expression and prostaglandin E2 (PGE2) production. Moreover, melamine activated NADPH oxidase (NOX), including NOX1, NOX2 and NOX4, accompanied with an increase in reactive oxygen species (ROS) production. Furthermore, melamine-induced ROS production could be attenuated by apocynin, a NOX inhibitor. In conclusion, our findings suggest melamine increased inflammation and oxidative stress via activation of NF-κB/COX-2 and NOX/ROS pathway, and first revealed the critical role of NOX in melamine-induced ROS production, suggesting the potential of NOX inhibitor against melamine toxicity.