Interleukin 4 is inactivated via selective disulfide-bond reduction by extracellular thioredoxin.

ABSTRACT: Thioredoxin 1 (TRX), an essential intracellular redox regulator, is also secreted by mammalian cells. Recently, we showed that TRX activates extracellular transglutaminase 2 via reduction of an allosteric disulfide bond. In an effort to identify other extracellular substrates of TRX, macrophages derived from THP-1 cells were treated with NP161, a small-molecule inhibitor of secreted TRX. NP161 enhanced cytokine outputs of alternatively activated macrophages, suggesting that extracellular TRX regulated the activity of interleukin 4 (IL-4) and/or interleukin 13 (IL-13). To test this hypothesis, the C35S mutant of human TRX was shown to form a mixed disulfide bond with recombinant IL-4 but not IL-13. Kinetic analysis revealed a k_cat/K_M value of 8.1 μM^-

SUBMITTER: Plugis NM 

PROVIDER: S-EPMC6126747 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature