Acute Ochratoxin A exposure induces inflammation and apoptosis in human embryonic kidney (HEK293) cells.

Ochratoxin A (OTA), a common contaminant of grain and fruit and known carcinogen, has been linked to impaired antioxidant response and cellular repair. The effect of OTA on inflammation in cells has not been explored. This study investigated OTA's influence on inflammatory mediators using a range of OTA concentrations (0.5 μM (sub-IC), 1.2 μm (IC) and 2 μm (supra-IC)) on human embryonic kidney (HEK293) cells over 24hr. The markers of inflammation in HEK293 cells were evaluated using the following techniques: western blotting (phosphorylated (p-)NFκB (Ser536), p-IKK (Ser176/180) and p-p53 (Ser392), total NFκB, IKK, IκBα and p53), luminometry (caspases 1, 3/7, 8, 9, ATP) and ELISA to determine IL-1β levels. The results indicate increased activation of the inflammatory pathway in the sub-IC concentration, evidenced by significant increases in p-NFκB (p = 0.0006). The IC concentration indicates decreased inflammatory induction supported by decreased levels of IL-1β and caspase 1 (p = 0.0186 and p = 0.0068 respectively) with decreased IKK and increased IκBα (p = 0.0046 and p = 0.0006 respectively). Furthermore, a decrease in inflammatory pathway activation was seen in O3 (increased IκBα, p < 0.05) coupled with increased apoptosis via elevated caspase 3/7 (p = 0.0002), 8 (p = 0.0011) and 9 activity (p = 0.0002); as well as decreased ATP levels. This data suggests a new mechanism of OTA toxicity and its involvement in inflammation, kidney disease and fibrosis.