3.4.1 Eosinophils
Excessive proliferation and infiltration of eosinophils is generally considered to be a marker of allergic inflammatory conditions. Trx1 inhibits the migration and activation of eosinophils by regulating the extracellular Th1/Th2 balance, cellular signalling pathway and molecules that interact with EOS-produced cytokines. In allergic asthma, Trx1 inhibits eosinophil accumulation by inducing Th1 cytokine production and suppressing Th2 cytokine production.22 Low expression of MIF in the airway of Trx1-Tg mice significantly inhibits eosinophil aggregation and mucus metaplasia.24 In addition, MIF can directly induce the production of eotaxin to promote eosinophil chemotaxis;78 however, as described earlier, Trx1 can bind to MIF inside and outside cells to block its internalisation and pro-inflammatory activity. Eotaxin, which is an eosinophil chemotactic chemokine, is mediated by C-C chemokine receptor type 3 (CCR3) on the surface of eosinophils.79 Eotaxin-stimulated eosinophils incubated with Trx1 significantly reduce the activation of eotaxin-stimulated ERK1/2 and p38MAPK pathways,80-82but Trx1 does not affect CCR3 expression in eosinophils; thus, chemokine-induced eosinophil migration is apparently attenuated by regulating the downstream signalling of CCR3. In addition, intraperitoneal injection of Trx1 has been shown to significantly reduce the overproduction of MIP-1α and IL-13, which is closely related to eosinophil chemotaxis in the lungs.23 In vitrostudies have confirmed that Trx1-overexpressing human bronchial epithelial cells can be protected from damage caused by eosinophils.83 Furthermore, Trx1 directly suppresses the production of ROS in eosinophils.84 Overall, Trx1 exerts anti-allergic effects by regulating eosinophil activation and migration (Figure 1b).