Curcumin has been reported to correct cystic fibrosis caused by the Delta F508 mutation of the cystic fibrosis transmembrane regulator (CFTR) but its mechanistic action remains unclear. We have recently demonstrated that the ER chaperone calreticulin (CRT) negatively regulates the CFTR cell surface expression and activity. Thus, we aimed at determining whether CRT mediates the effect of curcumin on CFTR. We show here that the treatment with curcumin of Chinese hamster ovary cells suppressed CRT expression and increased wildtype CFTR but did not affect Delta F508 CFTR expression. However, we determined that although curcumin did not augment Delta F508 CFTR expression, it enhanced the functional competence of Delta F508 CFTR induced by 26 degrees C incubation. Knock down of CRT by siRNA at low-temperature had a similar effect. Our findings suggest that the positive effect of curcumin on CFTR expression is mediated through the down-regulation of CRT, a negative regulator of CFTR. (c) 2006 Elsevier Inc. All rights reserved.