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)

P T van Hal, J P Hopstaken-Broos, A Prins, E J Favaloro, R J Huijbens, C Hilvering, C G Figdor, H C Hoogsteden

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46 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2718-28
Number of pages11
JournalJournal of Immunology
Volume153
Issue number6
Publication statusPublished - 15 Sep 1994

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