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Targeting airway inflammation: PMX464 and the epithelial bulls eye
Author(s) -
Sexton D W
Publication year - 2008
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/bjp.2008.290
Subject(s) - thioredoxin , thioredoxin reductase , microbiology and biotechnology , gene knockdown , biology , inflammation , a549 cell , immunology , cancer research , apoptosis , oxidative stress , endocrinology , biochemistry
Increasing evidence places the epithelial cell at the centre of inflammatory processes in human airways. Crucial to this function and the maintenance of inflammatory homoeostasis is a balanced oxidant–antioxidant status in the airway, in part controlled by thioredoxin and thioredoxin reductase, which together can alter the NF‐κB pathway. PMX464, a thiol‐reactive quinol and putative thioredoxin inhibitor, has been investigated in endothelial cells, fibroblasts and colorectal cancer cell lines but in the present issue of the BJP , these investigations were extended to A549 airway epithelial cells. Thioredoxin inhibition was confirmed as was NF‐κB and IKK suppression but siRNA knockdown of thioredoxin did not alter inflammatory marker expression or activity, suggesting that PMX464 has targets other than thioredoxin. Future consolidation of this evidence will involve concomitant knockdown of thioredoxin reductase, the use of primary airway epithelial cells and, potentially, the employment of three‐dimensional (3D) culture systems for both A549 and primary cells. British Journal of Pharmacology (2008) 155 , 620–622; doi: fn1 ; published online 7 July 2008