Oxidation of IκBα at methionine 45 is one cause of taurine chloramine-induced inhibition of NF-κB activation.

A band shift of IkappaBalpha was observed in Western blots with Jurkat cells treated with I nM taurine chloramine (TauCl) for I h. TauC1 treatment inhibited tumor necrosis factor a (TNFalpha)-initiated nuclear factor kappaB (NF-kappaB) activation. TauCl did not inhibit either the upstream of IkappaB kinase (IKK) activation or IKK itself but did inhibit NF-kappaB activation induced by IKK overexpression. Deletion experiments showed that a TauCl modification site causing the band shift of IkappaBalpha is Met(45). High performance liquid chromatography and mass spectrometry analyses of a small peptide containing Met4(5) revealed that TauC1 oxidizes Met45. A mutant of IkappaBalpha whose Met(45) was converted to alanine did not generate a band shift upon TauC1 treatment and degraded in response to TNFalpha stimulation. However, a reporter assay revealed that NF-kappaB-dependent luciferase expression was not fully recovered in cells transfected with this mutant. These results indicate that Met(45) oxidation of IkappaBalpha is a molecular mechanism underlying the TauCl-induced inhibition of NF-kappaB activation. A similar band shift was observed when HL-60 cells expressing myeloperoxidase were treated with 100 muM hydrogen peroxide for 5 min. When rat neutrophils were incubated with bacteria, intracellular taurine decreased interleukin-8 production. Therefore, taurine may help suppress excessive inflammatory reaction in neutrophils.