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

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

Cite this

Scotton, Chris J ; Martinez, Fernando O ; Smelt, Maaike J ; Sironi, Marina ; Locati, Massimo ; Mantovani, Alberto ; Sozzani, Silvano. / Transcriptional profiling reveals complex regulation of the monocyte IL-1 beta system by IL-13. In: Journal of immunology (Baltimore, Md. : 1950). 2005 ; Vol. 174, No. 2. pp. 834-845.
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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.",
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Transcriptional profiling reveals complex regulation of the monocyte IL-1 beta system by IL-13. / Scotton, Chris J; Martinez, Fernando O; Smelt, Maaike J; Sironi, Marina; Locati, Massimo; Mantovani, Alberto; Sozzani, Silvano.

In: Journal of immunology (Baltimore, Md. : 1950), Vol. 174, No. 2, 15.01.2005, p. 834-845.

Research output: Contribution to journalArticleAcademicpeer-review

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AB - 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.

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KW - RNA, Messenger/antagonists & inhibitors

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