IL-22 is induced by S100/calgranulin and impairs cholesterol efflux in macrophages by downregulating ABCG1

S100A8/9 and S100A12 are emerging biomarkers for disease activity of autoimmune and cardiovascular diseases. We demonstrated previously that S100A12 accelerates atherosclerosis accompanied by large cholesterol deposits in atherosclerotic lesions of apoE-null mice. The objective of this study was to...

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Main Authors: Bijoy Chellan, Ling Yan, Timothy J. Sontag, Catherine A. Reardon, Marion A. Hofmann Bowman
Format: Article
Language:English
Published: Elsevier 2014-03-01
Series:Journal of Lipid Research
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0022227520376781
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spelling doaj-62331156346b45fe9f167a42ab180a9a2021-04-28T06:02:26ZengElsevierJournal of Lipid Research0022-22752014-03-01553443454IL-22 is induced by S100/calgranulin and impairs cholesterol efflux in macrophages by downregulating ABCG1Bijoy Chellan0Ling Yan1Timothy J. Sontag2Catherine A. Reardon3Marion A. Hofmann Bowman4Departments of Medicine University of Chicago, Chicago, ILDepartments of Medicine University of Chicago, Chicago, ILPathology, University of Chicago, Chicago, ILPathology, University of Chicago, Chicago, ILTo whom correspondence should be addressed; Departments of Medicine University of Chicago, Chicago, ILS100A8/9 and S100A12 are emerging biomarkers for disease activity of autoimmune and cardiovascular diseases. We demonstrated previously that S100A12 accelerates atherosclerosis accompanied by large cholesterol deposits in atherosclerotic lesions of apoE-null mice. The objective of this study was to ascertain whether S100/calgranulin influences cholesterol homeostasis in macrophages. Peritoneal macrophages from transgenic mice expressing human S100A8/9 and S100A12 in myeloid cells [human bacterial artificial chromosome (hBAC)/S100] have increased lipid content and reduced ABCG1 expression and [3H]cholesterol efflux compared with WT littermates. This was associated with a 6-fold increase in plasma interleukin (IL)-22 and increased IL-22 mRNA in splenic T cells. These findings are mediated by the receptor for advanced glycation endproducts (RAGE), because hBAC/S100 mice lacking RAGE had normal IL-22 expression and normal cholesterol efflux. In vitro, recombinant IL-22 reduced ABCG1 expression and [3H]cholesterol efflux in THP-1 macrophages, while recombinant S100A12 had no effect on ABCG1 expression. In conclusion, S100/calgranulin has no direct effect on cholesterol efflux in macrophages, but rather promotes the secretion of IL-22, which then directly reduces cholesterol efflux in macrophages by decreasing the expression of ABCG1.http://www.sciencedirect.com/science/article/pii/S0022227520376781cholesterol transportersS100A12receptor for advanced glycation endproductsperitoneal macrophagesinterleukin-22
collection DOAJ
language English
format Article
sources DOAJ
author Bijoy Chellan
Ling Yan
Timothy J. Sontag
Catherine A. Reardon
Marion A. Hofmann Bowman
spellingShingle Bijoy Chellan
Ling Yan
Timothy J. Sontag
Catherine A. Reardon
Marion A. Hofmann Bowman
IL-22 is induced by S100/calgranulin and impairs cholesterol efflux in macrophages by downregulating ABCG1
Journal of Lipid Research
cholesterol transporters
S100A12
receptor for advanced glycation endproducts
peritoneal macrophages
interleukin-22
author_facet Bijoy Chellan
Ling Yan
Timothy J. Sontag
Catherine A. Reardon
Marion A. Hofmann Bowman
author_sort Bijoy Chellan
title IL-22 is induced by S100/calgranulin and impairs cholesterol efflux in macrophages by downregulating ABCG1
title_short IL-22 is induced by S100/calgranulin and impairs cholesterol efflux in macrophages by downregulating ABCG1
title_full IL-22 is induced by S100/calgranulin and impairs cholesterol efflux in macrophages by downregulating ABCG1
title_fullStr IL-22 is induced by S100/calgranulin and impairs cholesterol efflux in macrophages by downregulating ABCG1
title_full_unstemmed IL-22 is induced by S100/calgranulin and impairs cholesterol efflux in macrophages by downregulating ABCG1
title_sort il-22 is induced by s100/calgranulin and impairs cholesterol efflux in macrophages by downregulating abcg1
publisher Elsevier
series Journal of Lipid Research
issn 0022-2275
publishDate 2014-03-01
description S100A8/9 and S100A12 are emerging biomarkers for disease activity of autoimmune and cardiovascular diseases. We demonstrated previously that S100A12 accelerates atherosclerosis accompanied by large cholesterol deposits in atherosclerotic lesions of apoE-null mice. The objective of this study was to ascertain whether S100/calgranulin influences cholesterol homeostasis in macrophages. Peritoneal macrophages from transgenic mice expressing human S100A8/9 and S100A12 in myeloid cells [human bacterial artificial chromosome (hBAC)/S100] have increased lipid content and reduced ABCG1 expression and [3H]cholesterol efflux compared with WT littermates. This was associated with a 6-fold increase in plasma interleukin (IL)-22 and increased IL-22 mRNA in splenic T cells. These findings are mediated by the receptor for advanced glycation endproducts (RAGE), because hBAC/S100 mice lacking RAGE had normal IL-22 expression and normal cholesterol efflux. In vitro, recombinant IL-22 reduced ABCG1 expression and [3H]cholesterol efflux in THP-1 macrophages, while recombinant S100A12 had no effect on ABCG1 expression. In conclusion, S100/calgranulin has no direct effect on cholesterol efflux in macrophages, but rather promotes the secretion of IL-22, which then directly reduces cholesterol efflux in macrophages by decreasing the expression of ABCG1.
topic cholesterol transporters
S100A12
receptor for advanced glycation endproducts
peritoneal macrophages
interleukin-22
url http://www.sciencedirect.com/science/article/pii/S0022227520376781
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