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ID 113532
Title Alternative
Aromatase Controls Sjögren’s Syndrome-like Lesions through MCP-1 in Target Organ and Adipose Tissue-Associated Macrophages
A Role of Aromatase in Sjögren Syndrome
Author
Arakaki, Rieko The University of Tokushima KAKEN Search Researchers
Honma, Naoko Tokyo Metropolitan Institute of Gerontology
Yamada, Akiko The University of Tokushima KAKEN Search Researchers
Kurosawa, Emi The University of Tokushima
Kujiraoka, Satoko The University of Tokushima
Yoshimura, Noriko Fujita Health University
Harada, Nobuhiro Fujita Health University
Content Type
Journal Article
Description
Several autoimmune diseases are known to develop in postmenopausal women. However, the mechanism by which estrogen deficiency influences autoimmunity is unknown. Aromatase is a converting enzyme from androgens to estrogens. In the present study, we used female aromatase gene knockout (ArKO) mice as a model of estrogen deficiency to investigate the molecular mechanism that underlies the onset and development of autoimmunity. Histological analyses showed that inflammatory lesions in the lacrimal and salivary glands of ArKO mice increased with age. Adoptive transfer of spleen cells or bone marrow cells from ArKO mice into recombination activating gene 2 knockout mice failed to induce the autoimmune lesions. Expression of mRNA encoding proinflammatory cytokines and monocyte chemotactic protein-1 (MCP-1) increased in white adipose tissue (WAT) of ArKO mice and was significantly higher than that in wild-type mice. Moreover, an increased number of inflammatory M-1 macrophage was observed in WAT of ArKO mice. A significantly increased MCP-1 mRNA expression of the salivary gland tissue in ArKO was found together with adiposity. Furthermore, the autoimmune lesions in a murine model of Sjögren’s syndrome (SS) were exacerbated by administration of an aromatase inhibitor. These results suggest that aromatase may play in a key role in the pathogenesis of SS-like lesions by controlling the target organ and adipose tissue-associated macrophage.
Journal Title
The American Journal of Pathology
ISSN
00029440
15252191
NCID
AA00520990
AA12024839
Publisher
American Society for Investigative Pathology|Elsevier
Volume
185
Issue
1
Start Page
151
End Page
161
Published Date
2014-10-31
Rights
© 2014. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
Author
departments
Oral Sciences
Medical Sciences