Potential indirect anti-inflammatory 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).
IL-4 up-regulates various monocytic properties that are associated with pro-inflammatory functions. Paradoxically, IL-4 may also act as an anti-inflammatory agent by down-regulating the production of several inflammatory mediators. As the activity of some mediators has recently been shown to be regulated by peptidases, we examined whether IL-4 was able to modulate the expression of a cell membrane-associated peptidase, aminopeptidase-N (CD13). IL-4 caused a dose-dependent increase in the expression of CD13 Ag on highly purified human blood monocytes. Maximal 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 levels of CD13, which was maximal around 24 h of culture. We also observed that CD13-mediated leucine-aminopeptidase activity of monocytes was induced 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 human alveolar macrophages and endothelial cells upon IL-4 treatment. The increased expression of cell membrane aminopeptidase-N represents a potentially increased cellular ability to inactivate inflammatory mediators. Therefore, these findings represent further evidence of IL-4-mediated anti-inflammatory actions. We postulate that up-regulation of aminopeptidase-N expression may be an indirect mechanism of IL-4 to modulate the action of bioactive peptides. This mechanism may underlie, at least partially, the anti-inflammatory effects of IL-4 in vivo.
van Hal
P T
PT
Department of Immunology, Erasmus University, Rotterdam, The Netherlands.
Hopstaken-Broos
J P
JP
Prins
A
A
Favaloro
E J
EJ
Huijbens
R J
RJ
Hilvering
C
C
Figdor
C G
CG
Hoogsteden
H C
HC
D000626:Aminopeptidases / Q000096:biosynthesis* / Q000187:drug effects; D015703:Antigens, CD / Q000096:biosynthesis*; D015214:Antigens, Differentiation, Myelomonocytic / Q000096:biosynthesis*; D015152:Blotting, Northern; D018826:CD13 Antigens; D002460:Cell Line; D002478:Cells, Cultured; D016207:Cytokines / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology / Q000201:enzymology*; D006801:Humans; D015847:Interleukin-4 / Q000502:physiology*; D007931:Leucyl Aminopeptidase / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000201:enzymology*; D009000:Monocytes / Q000201:enzymology*; D012333:RNA, Messenger / Q000096:biosynthesis; D015854:Up-Regulation
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D016207:Cytokines; D012333:RNA, Messenger; D015847:Interleukin-4; D000626:Aminopeptidases; D007931:Leucyl Aminopeptidase; D018826:CD13 Antigens