Metabolism of haem in Caco-2 cells

The haem oxygenase-1-biliverdin reductase system degrades haem and generates biliverdin and bilirubin, both of which possess antioxidant and anti-inflammatory properties. Biliverdin and bilirubin are protective in intestinal injury models, but little is known about their generation and fate in the intestine. In the present work, an in vitro intestinal epithelial cell model, Caco-2 cells, were exposed to haem from either the apical or the basolateral side, and bile pigment generation and transport were measured spectrophotometrically and with high-pressure liquid chromatography. The Caco-2 cells generated bilirubin and bilirubin glucuronides upon exposure to haem. Bilirubin appeared predominantly in the apical medium regardless of the side to which haem was applied. In contrast to an earlier report, significant bidirectional haem transport was not observed. We conclude that Caco-2 cells metabolize haem and export its metabolic product, bilirubin, principally to the lumen, where it may exert antioxidant and anti-inflammatory functions.