Accumulation of CD11c+CD163+ Adipose Tissue Macrophages through Upregulation of Intracellular 11β-HSD1 in Human Obesity
Adipose tissue (AT) macrophages (ATMs) are key players for regulation of AT homeostasis and obesity-related metabolic disorders. However, the phenotypes of human ATMs and regulatory mechanisms of their polarization have not been clearly described. In this study, we investigated human ATMs in both abdominal visceral AT and s.c. AT and proposed an 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1)–glucocorticoid receptor regulatory axis that might dictate M1/M2 polarization in ATMs. The accumulation of CD11c + CD163 + ATMs in both visceral AT and s.c. AT of obese individuals was confirmed at the cellular level and was found to be clearly correlated with body mass index and production of reactive oxygen species. Using our in vitro system where human peripheral blood monocytes (hPBMs) were cocultured with Simpson–Golabi–Behmel syndrome adipocytes, M1/M2 polarization was found to be dependent on 11β-HSD1, an intracellular glucocorticoid reactivating enzyme. Exposure of hPBMs to cortisol-induced expression of CD163 and RU-486, a glucocorticoid receptor antagonist, significantly abrogated CD163 expression through coculture of mature adipocytes with hPBMs. Moreover, 11β-HSD1 was expressed in crown ATMs in obese AT. Importantly, conditioned medium from coculture of adipocytes with hPBMs enhanced proliferation of human breast cancer MCF7 and MDA-MB-231 cells. In summary, the phenotypic switch of ATMs from M2 to mixed M1/M2 phenotype occurred through differentiation of adipocytes in obese individuals, and upregulation of intracellular 11β-HSD1 might play a role in the process.
- DOI : http://dx.doi.org/10.4049/jimmunol.1600895
- American Association of Immunologists : 저널> 권호 > http://www.jimmunol.org/content/197/9/3735.abstract
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