Kinetics of IL-10-induced gene expression in human macrophages.
IL-10 is a strong inhibitor of macrophage (M(phi)) activation and inflammatory cytokine and chemokine production. To gain insight into mechanisms by which IL-10 suppresses inflammation, we performed a kinetic analysis of IL-10-induced gene expression in primary human M(phi). IL-10 induced rapid and transient expression of genes encoding transcription factors, followed by sustained elevation or suppression of gene expression. IL-10 suppressed basal expression of interferon-inducible genes, suggesting that IL-10 interrupts autocrine interferon-mediated priming. IL-10 induced the expression of prostaglandin dehydrogenase (PGDH), the major catabolic enzyme involved in prostaglandin degradation. Concomitant with PGDH expression, IL-10 induced increased degradation of the inflammatory PGE2 and suppressed PGE2-mediated effects on M(phi) morphology and gene expression. These results identify catabolism of inflammatory PGs as a mechanism of IL-10 anti-inflammatory action.
Antoniv
Taras T
TT
Arthritis and Tissue Degeneration Program, Department of Medicine, Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021, USA.
Park-Min
Kyung-Hyun
KH
Ivashkiv
Lionel B
LB
D015232:Dinoprostone / Q000276:immunology / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D007700:Kinetics; D008262:Macrophage Activation / Q000187:drug effects / Q000276:immunology; D008264:Macrophages / Q000187:drug effects* / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D012333:RNA, Messenger; D016753:Interleukin-10; D015232:Dinoprostone