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).