<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="6.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Fujihara, Satoko</style></author><author><style face="normal" font="default" size="100%">Ward, Carol</style></author><author><style face="normal" font="default" size="100%">Dransfield, Ian</style></author><author><style face="normal" font="default" size="100%">Hay, Ronald T</style></author><author><style face="normal" font="default" size="100%">Uings, Iain J</style></author><author><style face="normal" font="default" size="100%">Hayes, Brian</style></author><author><style face="normal" font="default" size="100%">Farrow, Stuart N</style></author><author><style face="normal" font="default" size="100%">Haslett, Christopher</style></author><author><style face="normal" font="default" size="100%">Rossi, Adriano G</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Inhibition of nuclear factor-kappaB activation un-masks the ability of TNF-alpha to induce human eosinophil apoptosis.</style></title><secondary-title><style face="normal" font="default" size="100%">European journal of immunology</style></secondary-title></titles><dates><year><style  face="normal" font="default" size="100%">2002</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2002 Feb</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">32</style></volume><pages><style face="normal" font="default" size="100%">457-66</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">Apoptosis renders eosinophils functionally effete and marks them for &quot;silent&quot; removal from inflamed sites by macrophages. We show, for the first time, that eosinophils exposed to TNF-alpha rapidly lose their cytoplasmic levels of IkappaBalpha, the inhibitory subunit of NF-kappaB. Consequently, TNF-alpha triggers NF-kappaB mobilization from the cytoplasm to the nucleus, as determined by tracking the NF-kappaB subunit p65 by immunofluorescence and Western blot analysis. Inhibition of TNF-alpha-mediated IkappaBalpha degradation and NF-kappaB activation by gliotoxin or the proteasome inhibitor MG-132 un-masks the caspase-dependent pro-apoptotic properties of TNF-alpha. In addition, cycloheximide similarly renders TNF-alpha pro-apoptotic, suggesting that NF-kappaB activation controls the production of a protein(s) that protects eosinophils from the cytotoxic effects of TNF-alpha. Evidence is presented suggesting that TNF-alpha triggered apoptosis is more susceptible to NF-kappaB inhibition than constitutive apoptosis, leading to the possibility of the specific targeting of apoptosis in eosinophil sub-populations. Prior to morphological signs of apoptosis, TNF-alpha-induced IL-8 synthesis is abrogated by inhibition of NF-kappaB. We propose that NF-kappaB activation plays a critical role in controlling eosinophil responsiveness and apoptosis, and speculate that selective inhibitors of eosinophil NF-kappaB activation may ultimately provide alternative therapeutic agents for the treatment of eosinophilic diseases, including asthma and allergic rhinitis.</style></abstract></record></records></xml>