Gliadin increases iNOS gene expression in interferon-γ-stimulated RAW 264.7 cells through a mechanism involving NF-κB.

Nitric oxide (NO) plays an important role in the pathogenesis of the histological changes seen in coeliac disease. We have investigated the effect of peptic-tryptic digest of gliadin (Pt-G) and gliadin (G) on inducible nitric oxide synthase (iNOS) protein expression in RAW 264.7 macrophages stimulated with interferon-γ (IFN-γ). Pt-G and G enhanced in a concentration and time-dependent manner NO production by IFN-γ-stimulated RAW 264.7 cells. The increase of iNOS protein expression was correlated with NF-κB/DNA binding activity and occurred at transcriptional level. Pyrrolidine dithiocarbamate and N-α-para-tosyl-L-lysine chloromethyl ketone, two known inhibitors of NF-κB activation, decreased significantly NO production and iNOS protein expression as well as NF-κB/DNA binding activity. Our results show that the effect of Pt-G and G on enhancement of iNOS protein expression in IFN-γ-treated RAW 264.7 cells is mainly mediated through NF-κB and suggest that blockage of NF-κB activation reduces enhancing effect of gluten on NO production in inflamed mucosa of coeliac patients. [ABSTRACT FROM AUTHOR]