POTENTIAL INDIRECT ANTIINFLAMMATORY EFFECTS OF IL-4 - STIMULATION OF HUMAN MONOCYTES, MACROPHAGES, AND ENDOTHELIAL-CELLS BY IL-4 INCREASES AMINOPEPTIDASE-N ACTIVITY (CD13 EC-3.4.11.2)
Ptw. Vanhal et al., POTENTIAL INDIRECT ANTIINFLAMMATORY EFFECTS OF IL-4 - STIMULATION OF HUMAN MONOCYTES, MACROPHAGES, AND ENDOTHELIAL-CELLS BY IL-4 INCREASES AMINOPEPTIDASE-N ACTIVITY (CD13 EC-3.4.11.2), The Journal of immunology, 153(6), 1994, pp. 2718-2728
IL-4 up-regulates various monocytic properties that are associated wit
h pro-inflammatory functions. Paradoxically, IL-4 may also act as an a
nti-inflammatory agent by down-regulating the production of several in
flammatory mediators. As the activity of some mediators has recently b
een shown to be regulated by peptidases, we examined whether IL-4 was
able to modulate the expression of a cell membrane-associated peptidas
e, aminopeptidase-N (CD13). IL-4 caused a dose-dependent increase in t
he expression of CD13 Ag on highly purified human blood monocytes. Max
imal expression was observed around 48 h of culture. This IL-4-induced
increase was completely blocked by anti-IL-4 antiserum. Furthermore,
the increase in surface expression was preceded by increased mRNA leve
ls of CD13, which was maximal around 24 h of culture. We also observed
that CD13-mediated leucine-aminopeptidase activity of monocytes was i
nduced by IL-4. Other CD13-expressing cells were also sensitive to IL-
4, as CD13 Ag expression and CD13 mRNA levels were up-regulated in hum
an alveolar macrophages and endothelial cells upon IL-4 treatment. The
increased expression of cell membrane aminopeptidase-N represents a p
otentially increased cellular ability to inactivate inflammatory media
tors. Therefore, these findings represent further evidence of IL-4-med
iated anti-inflammatory actions. We postulate that up-regulation of am
inopeptidase-N expression may be an indirect mechanism of IL-4 to modu
late the action of bioactive peptides. This mechanism may underlie, at
least partially, the anti-inflammatory effects of IL-4 in vivo.