Modification of IkappaBalpha by taurine bromamine inhibits tumor necrosis factor alpha-induced NF-kappaB activation.
OBJECTIVE
Eosinophils play a prominent role in the pathogenesis of various common human allergic diseases, including asthma. Taurine chloramine (TauCl) and taurine bromamine (TauBr) are products of activated neutrophils and eosinophils. TauCl has strong anti-inflammatory properties. However, much less is known about TauBr. The aim of this study was to compare the anti-inflammatory capacity and membrane permeability of TauBr to those of TauCl.


METHODS
Jurkat cells (T-lymphocytes) and YJ cells (myeloid-committed eosinophils) were used throughout this in vitro study. Tumor necrosis factor (TNFalpha) was employed for activation of the cells. Degradation of the cytosolic NF-kappaB inhibitor protein (IkappaBalpha) was studied by Western blot analysis. Assessment of NF-kappaB DNA binding activity was performed by an electrophoretic mobility shift assay (EMSA).


RESULTS
TauBr inhibited degradation of IkappaBalpha and TNFalpha-induced NF-kappaB activation. TauBr exerted an anti-inflammatory effect by a similar process to that of TauCl. TauBr administered extracellularly in phosphate buffered saline (PBS) shifted the IkappaBalpha band at a relatively low concentration of 50 muM. In addition, TauBr was membrane-permeable as demonstrated by the inactivation of glyceraldehyde-3-phosphate dehydrogenase (GAPDH).


CONCLUSIONS
TauBr was found to be highly membrane-permeable. TauBr might be generated both extracellularly and intracellularly by eosinophils at inflammatory sites in allergic disease and play an anti-inflammatory role.
Tokunaga
S
S
Department of Integrated Biosciences, Graduate School of Frontier Sciences, University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8562, Japan. kk27521@mail.ecc.u-tokyo.ac.jp
Kanayama
A
A
Miyamoto
Y
Y
D002463:Cell Membrane Permeability; D004804:Eosinophils / Q000187:drug effects / Q000378:metabolism; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D051550:I-kappa B Kinase / Q000378:metabolism*; D019169:Jurkat Cells; D016328:NF-kappa B / Q000378:metabolism*; D010084:Oxidation-Reduction; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D013654:Taurine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D013861:Thiocyanates / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D016328:NF-kappa B; D013861:Thiocyanates; D014409:Tumor Necrosis Factor-alpha; C517667:hypothiocyanous acid; D013654:Taurine; C043410:N-chlorotaurine; C052954:N-bromotaurine; D006861:Hydrogen Peroxide; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D051550:I-kappa B Kinase