IL-13 down-regulates CD14 expression and TNF-α secretion in normal human monocytes

G. Cosentino, E. Soprana, C. P. Thienes, A. G. Siccardi, G. Viale, D. Vercelli

Research output: Contribution to journalArticlepeer-review

82 Scopus citations

Abstract

CD14, a glycosylphosphatidylinositol (GPI)-linked protein expressed on monocytes and neutrophils, regulates monocyte-lymphocyte interactions and serves as the LPS receptor. We showed previously that IL-4 down-regulates the expression of human CD14 by acting at the transcriptional level. We now investigate whether CD14 expression could also be regulated by IL-13, another member of the chromosome 5 cytokine gene family. IL-13 dose-dependently inhibited CD14 expression on human monocytes. By contrast, expression of CD23 and CD11b was enhanced strongly. Down-regulation of CD14 involved neither shedding nor activation of endogenous GPI anchor-cleaving enzymes. Indeed, soluble CD14 was not increased in the supernatants of IL-13-stimulated monocytes, and expression of CD55/DAF, another GPI-linked protein, was unaffected by IL-13. CD14 transcript levels were reduced sixfold in IL-13- treated monocytes. These results suggest that IL-13 down-regulates membrane CD14 by suppressing CD14 RNA expression. IL-13-dependent down-regulation of CD14 resulted in the inhibition of CD14-mediated events. Indeed, CD14- mediated release of TNF-α was inhibited markedly (~75%) in monocytes stimulated with LPS (100 ng/ml) after a 72-h preincubation with IL-13. However, IL-13 also directly inhibited monokine secretion, because it blocked PMA-induced, CD14-independent TNF-α release. Down-regulation of CD14 and TNF-α secretion may play a major role in the anti-inflammatory effects of IL-13 on LPS-stimulated monocytes.

Original languageEnglish (US)
Pages (from-to)3145-3151
Number of pages7
JournalJournal of Immunology
Volume155
Issue number6
StatePublished - 1995
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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