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- 2017.1
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We evaluated the role of IL-10- in IL-33-mediated cholesterol reduction in macrophage-derived foam cells (MFCs) and the mechanism by which IL-33 upregulates IL-10. Serum IL-33 and IL-10 levels in coronary artery disease patients were measured.
The effects of IL-33 on intra-MFC cholesterol level, IL-10, ABCA1 and CD36 expression, ERK 1/2, Sp1, STAT3 and STAT4 activation, and IL-10 promoter activity were determined. Core sequences were identified using bioinformatic analysis and sitespecific mutagenesis. The serum IL-33 levels positively correlated with those of IL-10. IL-33 decreased cellular cholesterol level and upregulated IL-10 and ABCA1 but had no effect on CD36 expression. siRNA-IL-10 partially abolished cellular cholesterol reduction and ABCA1 elevation by IL-33 but did not reverse the decreased CD36 levels. IL-33 increased IL-10 mRNA production but had little effect on its stability. IL-33 induced ERK 1/2 phosphorylation and increased the luciferase expression driven by the IL-10 promoter, with the highest extent within the − 2000 to − 1752 bp segment of the 5′-flank of the transcription start site; these effects were counteracted by U0126. IL-33 activated Sp1, STAT3 and STAT4, but only the STAT3 binding site was predicted in the above segment. Site-directed mutagenesis of the predicted STAT3-binding sites (CTGCTTCCTGGCAGCAGAA→CTGCCTGGCAGCAGAA) reduced luciferase activity, and a STAT3 inhibitor blocked the regulatory effects of IL-33 on IL-10 expression. Chromatin immunoprecipitation (CHIP) confirmed the STAT3-binding sequences within the − 1997 to − 1700 and − 1091 to − 811 bp locus regions. IL-33 increased IL-10 expression in MFCs via activating ERK 1/2 and STAT3, which subsequently promoted IL-10 transcription and thus contributed to the beneficial effects of IL-33 on MFCs.
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참고문헌 (23)
참고문헌 신청
Brunner SM / 2011 / Interleukin-33 prolongs allograft survival during chronic cardiac rejection / Transpl Int 24 : 1027 ~ 1039
Foey AD / 2001 / CD40 ligation induces macrophage IL-10 and TNF-alpha production : differential use of the PI3K and p42/44MAPK-pathways / Cytokine 16 : 131 ~ 142
Han X / 2009 / Interleukin-10 facilitates both cholesterol uptake and efflux in macrophages / J Biol Chem 284 : 32950 ~ 32958
Kube D / 1995 / Isolation of the human interleukin 10 promoter. Characterization of the promoter activity in Burkitt’s lymphoma cell lines / Cytokine 7 : 1 ~ 7
Kurowska-Stolarska M / 2011 / Interleukin-33 : a novel mediator with a role in distinct disease pathologies / J Intern Med 269 : 29 ~ 35
Foey AD / 2001 / CD40 ligation induces macrophage IL-10 and TNF-alpha production : differential use of the PI3K and p42/44MAPK-pathways / Cytokine 16 : 131 ~ 142
Han X / 2009 / Interleukin-10 facilitates both cholesterol uptake and efflux in macrophages / J Biol Chem 284 : 32950 ~ 32958
Kube D / 1995 / Isolation of the human interleukin 10 promoter. Characterization of the promoter activity in Burkitt’s lymphoma cell lines / Cytokine 7 : 1 ~ 7
Kurowska-Stolarska M / 2011 / Interleukin-33 : a novel mediator with a role in distinct disease pathologies / J Intern Med 269 : 29 ~ 35
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