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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 publication

DOI

10.4049/jimmunol.174.2.834

Type

Journal article

Journal

Journal of immunology (Baltimore, Md. : 1950)

Publication Date

01/2005

Volume

174

Pages

834 - 845

Addresses

Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.

Keywords

Monocytes, Cells, Cultured, Humans, Caspase 1, Protein Precursors, RNA, Messenger, Interleukin-1, Interleukin-13, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Polymerase Chain Reaction, Macrophage Activation, Transcription, Genetic, Gene Expression Regulation, Hydrolysis, Caspase Inhibitors