Shaping gene expression in activated and resting primary macrophages by IL-10.
IL-10 regulates inflammation by reducing cytokine and chemokine production from activated macrophages. We performed microarray experiments to identify possible effector molecules of IL-10 and to investigate the global effect of IL-10 on the transcriptional response induced in LPS-activated macrophages. To exclude background effects of endogenous IL-10, macrophages from IL-10-deficient mice were used. IL-10 up-regulated expression of a small number of genes (26 and 37 after 45 min and 3 h, respectively), including newly identified and previously documented targets such as suppressor of cytokine signaling-3 and IL-1 receptor antagonist. However, the activation program triggered by LPS was profoundly affected by IL-10. IL-10 repressed 62 and further increased 15 of 259 LPS-induced genes. For all genes examined, the effects of IL-10 were determined to be STAT3-dependent. These results suggest that IL-10 regulates STAT3-dependent pathways that selectively target a broad component of LPS-induced genes at the mRNA level.
Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38015, USA.
Roland
R
Lang
Divyen
D
Patel
John J
JJ
Morris
Robert L
RL
Rutschman
Peter J
PJ
Murray
D000818:Animals; D001119:Arginase / Q000096:biosynthesis; D001854:Bone Marrow Cells / Q000166:cytology / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology*; D016753:Interleukin-10 / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015847:Interleukin-4 / Q000502:physiology; D007399:Interphase / Q000235:genetics / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000235:genetics* / Q000276:immunology; D008264:Macrophages / Q000166:cytology / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D019948:Receptors, Interleukin-4 / Q000096:biosynthesis; D050796:STAT3 Transcription Factor; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
D004268:DNA-Binding Proteins; D008070:Lipopolysaccharides; D019948:Receptors, Interleukin-4; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D015534:Trans-Activators; D016753:Interleukin-10; D015847:Interleukin-4; D001119:Arginase