Transcriptional profiling reveals complex regulation of the monocyte IL-1 beta system by IL-13.
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.
Scotton
Chris J
CJ
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Martinez
Fernando O
FO
Smelt
Maaike J
MJ
Sironi
Marina
M
Locati
Massimo
M
Mantovani
Alberto
A
Sozzani
Silvano
S
D020170:Caspase 1 / Q000096:biosynthesis; D061945:Caspase Inhibitors; D002478:Cells, Cultured; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D006868:Hydrolysis; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018793:Interleukin-13 / Q000502:physiology*; D008262:Macrophage Activation / Q000276:immunology; D009000:Monocytes / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D016133:Polymerase Chain Reaction / Q000379:methods; D011498:Protein Precursors / Q000037:antagonists & inhibitors / Q000378:metabolism; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D014158:Transcription, Genetic / Q000276:immunology*
D061945:Caspase Inhibitors; D007375:Interleukin-1; D018793:Interleukin-13; D011498:Protein Precursors; D012333:RNA, Messenger; D020170:Caspase 1