Modification of IκBα by taurine bromamine inhibits tumor necrosis factor α-induced NF-κB activation

Abstract.

Objective and design:

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.

Materials and methods:

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

Results:

TauBr inhibited degradation of IκBα and TNFα-induced NF-κB 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 IκBα band at a relatively low concentration of 50 μM. 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.