IL-13 down-regulates CD14 expression and TNF-alpha secretion in normal human monocytes.
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-alpha was inhibited markedly (approximately 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-alpha release. Down-regulation of CD14 and TNF-alpha secretion may play a major role in the anti-inflammatory effects of IL-13 on LPS-stimulated monocytes.
Cosentino
G
G
Molecular Immunoregulation Unit, DIBIT/San Raffaele Scientific Institute, Milan, Italy.
Soprana
E
E
Thienes
C P
CP
Siccardi
A G
AG
Viale
G
G
Vercelli
D
D
D015703:Antigens, CD / Q000096:biosynthesis*; D015214:Antigens, Differentiation, Myelomonocytic / Q000096:biosynthesis*; D001483:Base Sequence; D002478:Cells, Cultured; D015536:Down-Regulation; D006801:Humans; D018793:Interleukin-13 / Q000494:pharmacology*; D018950:Lipopolysaccharide Receptors; D008969:Molecular Sequence Data; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D016133:Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D018793:Interleukin-13; D018950:Lipopolysaccharide Receptors; D014409:Tumor Necrosis Factor-alpha