PMID:10975994

Citation	Raychaudhuri, B, Fisher, CJ, Farver, CF, Malur, A, Drazba, J, Kavuru, MS and Thomassen, MJ (2000) Interleukin 10 (IL-10)-mediated inhibition of inflammatory cytokine production by human alveolar macrophages. Cytokine 12:1348-55
Abstract	Alveolar macrophages are an important source of inflammatory cytokines in the lung. IL-10 has been shown to inhibit inflammatory cytokine production by human alveolar macrophages, but mechanisms are unclear. The purpose of the present study was to investigate whether IL-10 modified cytokine production by interference with transcriptional pathways. Alveolar macrophages were obtained from healthy controls by fiberoptic bronchoscopy and incubated with LPS+/-IL-10. Results indicated that steady state mRNA levels of tumour necrosis factor-alpha (TNF) and interleukin 1-beta (IL-1) decreased in the presence of IL-10. Consequently, electrophoretic mobility shift assays were performed using end-labelled nuclear factor-kappa B (NF-kappa B) or activator protein-1 (AP-1) probe. NF-kappa B binding was decreased in extracts from macrophages incubated for 4 h with LPS+IL-10 in comparison to those incubated with LPS alone. IL-10 also inhibited TNF secretion and NF-kappa B activation induced by another stimulus, staphylococcal toxin. Supershift assays revealed the presence of both p50 and p65 subunits of NF-kappa B. AP-1 was not affected by IL-10. Further examination of mechanisms indicated that IL-10 delayed the LPS-mediated degradation of the inhibitor protein I kappa B, thus delaying the nuclear translocation of the p65 subunit. These observations provide the first evidence that IL-10 antagonizes cytokine transcription in human alveolar macrophages by impeding the nuclear translocation of NF-kappa B by delaying the degradation of I kappa B.
Links	PubMed Online version:10.1006/cyto.2000.0721
Keywords	Blotting, Western; Cell Nucleus/metabolism; Cytokines/biosynthesis; Enterotoxins/metabolism; Humans; I-kappa B Proteins/metabolism; Interleukin-1/metabolism; Interleukin-10/pharmacology; Lipopolysaccharides/pharmacology; Lung/immunology; Macrophages, Alveolar/immunology; Macrophages, Alveolar/metabolism; Microscopy, Fluorescence; NF-kappa B/metabolism; RNA, Messenger/metabolism; Transcription Factor RelA; Transcription, Genetic; Tumor Necrosis Factor-alpha/metabolism
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:IL10	involved_in	GO:0007253: cytoplasmic sequestering of NF-kappaB	ECO:0000303: author statement without traceable support used in manual assertion		P		Seeded From UniProt	complete

References

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