Transcriptional profiling reveals complex regulation of the monocyte IL-1 beta system by IL-13

Chris J Scotton, Fernando O Martinez, Maaike J Smelt, Marina Sironi, Massimo Locati, Alberto Mantovani, Silvano Sozzani

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

IL-4 and IL-13 are prototypic Th2 cytokines that generate an "alternatively activated" phenotype in macrophages. We used high-density oligonucleotide microarrays to investigate the transcriptional profile induced in human monocytes by IL-13. After 8-h stimulation with IL-13, 142 genes were regulated (85 increased and 57 decreased). The majority of these genes were related to the inflammatory response and innate immunity; a group of genes related to lipid metabolism was also identified, with clear implications for atherosclerosis. In addition to characteristic markers of alternatively activated macrophages, a number of novel IL-13-regulated genes were seen. These included various pattern recognition receptors, such as CD1b/c/e, TLR1, and C-type lectin superfamily member 6. Several components of the IL-1 system were regulated. IL-1RI, IL-1RII, and IL-1Ra were all up-regulated, whereas the IL-1beta-converting enzyme, caspase 1, and IRAK-M were down-regulated. LPS-inducible caspase 1 enzyme activity was also reduced in IL-13-stimulated monocytes, with a consequent decrease in pro-IL-1beta processing. These data reveal that IL-13 has a potent effect on the transcriptional profile in monocytes. The IL-13-induced modulation of genes related to IL-1 clearly highlights the tightly controlled and complex levels of regulation of the production and response to this potent proinflammatory cytokine.

Original languageEnglish
Pages (from-to)834-845
JournalJournal of immunology (Baltimore, Md. : 1950)
Volume174
Issue number2
DOIs
Publication statusPublished - 15 Jan 2005

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Keywords

  • Caspase 1/biosynthesis
  • Caspase Inhibitors
  • Cells, Cultured
  • Gene Expression Profiling/methods
  • Gene Expression Regulation/immunology
  • Humans
  • Hydrolysis
  • Interleukin-1/antagonists & inhibitors
  • Interleukin-13/physiology
  • Macrophage Activation/immunology
  • Monocytes/enzymology
  • Oligonucleotide Array Sequence Analysis/methods
  • Polymerase Chain Reaction/methods
  • Protein Precursors/antagonists & inhibitors
  • RNA, Messenger/antagonists & inhibitors
  • Transcription, Genetic/immunology

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