Active Cushing disease is characterized by increased adipose tissue macrophage presence

Irene T. Lee; Alexandria Atuahene; Hale Ergin Egritag; Ling Wang; Michael Donovan; Christoph Buettner; Eliza B. Geer

doi:https://doi.org/10.1210/jc.2018-02552

Active Cushing disease is characterized by increased adipose tissue macrophage presence

Irene T. Lee, Alexandria Atuahene, Hale Ergin Egritag, Ling Wang, Michael Donovan, Christoph Buettner, Eliza B. Geer

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

Abstract

Context: Although glucocorticoids (GCs) have potent anti-inflammatory actions, patients with hypercortisolism due to Cushing disease (CD) have increased circulating proinflammatory cytokines that may contribute to their insulin resistance and cardiovascular disease. The mechanisms and tissues that account for the increased systemic inflammation in patients with CD are unknown. Objective: To determine whether chronic endogenous GC exposure due to CD is associated with adipose tissue (AT) inflammation in humans. Design, Setting, Participants: Abdominal subcutaneous AT samples from 10 patients with active CD and 10 age-, sex-, and body mass index?matched healthy subjects were assessed for macrophage infiltration and mRNA expression of proinflammatory cytokines. Main Outcome Measure: Using immunohistochemistry, AT samples were analyzed for the expression of vimentin, caspase, CD3, CD4, CD8, CD11c, CD20, CD31, CD56, CD68, and CD163. Quantitative PCR was used to assess the mRNA gene expression of arginase, CD11b, CD68, EMR-1, IL-6, IL-10, MCP-1, and TNF-a. Results: Immunohistochemistry revealed higher mean percentage infiltration of CD68⁺ macrophages and CD4⁺ T lymphocytes, increased mean area of CD11c⁺ M1 macrophages, higher number of CD11c⁺ crownlike structures, and decreased vimentin in the AT of patients with active CD compared with controls. PCR revealed no differences in mRNA expression of any analyzed markers in patients with CD. Conclusions: Chronic exposure to GCs due to CD increases the presence of AT macrophages, a hallmark of AT inflammation. Hence, AT inflammation may be the source of the systemic inflammation seen in CD, which in turn may contribute to obesity, insulin resistance, and cardiovascular disease in these patients.

Original language	American English
Pages (from-to)	2453-2461
Number of pages	9
Journal	Journal of Clinical Endocrinology and Metabolism
Volume	104
Issue number	6
DOIs	https://doi.org/10.1210/jc.2018-02552
State	Published - Jun 1 2019
Externally published	Yes

ASJC Scopus subject areas

Endocrinology, Diabetes and Metabolism
Biochemistry
Endocrinology
Clinical Biochemistry
Biochemistry, medical

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https://doi.org/10.1210/jc.2018-02552

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@article{12bdfb68a6cf4cefbaef139ea47f839d,

title = "Active Cushing disease is characterized by increased adipose tissue macrophage presence",

abstract = "Context: Although glucocorticoids (GCs) have potent anti-inflammatory actions, patients with hypercortisolism due to Cushing disease (CD) have increased circulating proinflammatory cytokines that may contribute to their insulin resistance and cardiovascular disease. The mechanisms and tissues that account for the increased systemic inflammation in patients with CD are unknown. Objective: To determine whether chronic endogenous GC exposure due to CD is associated with adipose tissue (AT) inflammation in humans. Design, Setting, Participants: Abdominal subcutaneous AT samples from 10 patients with active CD and 10 age-, sex-, and body mass index?matched healthy subjects were assessed for macrophage infiltration and mRNA expression of proinflammatory cytokines. Main Outcome Measure: Using immunohistochemistry, AT samples were analyzed for the expression of vimentin, caspase, CD3, CD4, CD8, CD11c, CD20, CD31, CD56, CD68, and CD163. Quantitative PCR was used to assess the mRNA gene expression of arginase, CD11b, CD68, EMR-1, IL-6, IL-10, MCP-1, and TNF-a. Results: Immunohistochemistry revealed higher mean percentage infiltration of CD68+ macrophages and CD4+ T lymphocytes, increased mean area of CD11c+ M1 macrophages, higher number of CD11c+ crownlike structures, and decreased vimentin in the AT of patients with active CD compared with controls. PCR revealed no differences in mRNA expression of any analyzed markers in patients with CD. Conclusions: Chronic exposure to GCs due to CD increases the presence of AT macrophages, a hallmark of AT inflammation. Hence, AT inflammation may be the source of the systemic inflammation seen in CD, which in turn may contribute to obesity, insulin resistance, and cardiovascular disease in these patients.",

author = "Lee, {Irene T.} and Alexandria Atuahene and Egritag, {Hale Ergin} and Ling Wang and Michael Donovan and Christoph Buettner and Geer, {Eliza B.}",

note = "Funding Information: Financial Support: This work was supported by National Institutes of Health grants K23 DK 082617 (to E.B.G.) and R01AA023416 and DK082724 (to C.B.). Publisher Copyright: Copyright {\textcopyright} 2019 Endocrine Society",

year = "2019",

month = jun,

day = "1",

doi = "https://doi.org/10.1210/jc.2018-02552",

language = "American English",

volume = "104",

pages = "2453--2461",

journal = "Journal of Clinical Endocrinology and Metabolism",

issn = "0021-972X",

publisher = "The Endocrine Society",

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TY - JOUR

T1 - Active Cushing disease is characterized by increased adipose tissue macrophage presence

AU - Lee, Irene T.

AU - Atuahene, Alexandria

AU - Egritag, Hale Ergin

AU - Wang, Ling

AU - Donovan, Michael

AU - Buettner, Christoph

AU - Geer, Eliza B.

N1 - Funding Information: Financial Support: This work was supported by National Institutes of Health grants K23 DK 082617 (to E.B.G.) and R01AA023416 and DK082724 (to C.B.). Publisher Copyright: Copyright © 2019 Endocrine Society

PY - 2019/6/1

Y1 - 2019/6/1

N2 - Context: Although glucocorticoids (GCs) have potent anti-inflammatory actions, patients with hypercortisolism due to Cushing disease (CD) have increased circulating proinflammatory cytokines that may contribute to their insulin resistance and cardiovascular disease. The mechanisms and tissues that account for the increased systemic inflammation in patients with CD are unknown. Objective: To determine whether chronic endogenous GC exposure due to CD is associated with adipose tissue (AT) inflammation in humans. Design, Setting, Participants: Abdominal subcutaneous AT samples from 10 patients with active CD and 10 age-, sex-, and body mass index?matched healthy subjects were assessed for macrophage infiltration and mRNA expression of proinflammatory cytokines. Main Outcome Measure: Using immunohistochemistry, AT samples were analyzed for the expression of vimentin, caspase, CD3, CD4, CD8, CD11c, CD20, CD31, CD56, CD68, and CD163. Quantitative PCR was used to assess the mRNA gene expression of arginase, CD11b, CD68, EMR-1, IL-6, IL-10, MCP-1, and TNF-a. Results: Immunohistochemistry revealed higher mean percentage infiltration of CD68+ macrophages and CD4+ T lymphocytes, increased mean area of CD11c+ M1 macrophages, higher number of CD11c+ crownlike structures, and decreased vimentin in the AT of patients with active CD compared with controls. PCR revealed no differences in mRNA expression of any analyzed markers in patients with CD. Conclusions: Chronic exposure to GCs due to CD increases the presence of AT macrophages, a hallmark of AT inflammation. Hence, AT inflammation may be the source of the systemic inflammation seen in CD, which in turn may contribute to obesity, insulin resistance, and cardiovascular disease in these patients.

AB - Context: Although glucocorticoids (GCs) have potent anti-inflammatory actions, patients with hypercortisolism due to Cushing disease (CD) have increased circulating proinflammatory cytokines that may contribute to their insulin resistance and cardiovascular disease. The mechanisms and tissues that account for the increased systemic inflammation in patients with CD are unknown. Objective: To determine whether chronic endogenous GC exposure due to CD is associated with adipose tissue (AT) inflammation in humans. Design, Setting, Participants: Abdominal subcutaneous AT samples from 10 patients with active CD and 10 age-, sex-, and body mass index?matched healthy subjects were assessed for macrophage infiltration and mRNA expression of proinflammatory cytokines. Main Outcome Measure: Using immunohistochemistry, AT samples were analyzed for the expression of vimentin, caspase, CD3, CD4, CD8, CD11c, CD20, CD31, CD56, CD68, and CD163. Quantitative PCR was used to assess the mRNA gene expression of arginase, CD11b, CD68, EMR-1, IL-6, IL-10, MCP-1, and TNF-a. Results: Immunohistochemistry revealed higher mean percentage infiltration of CD68+ macrophages and CD4+ T lymphocytes, increased mean area of CD11c+ M1 macrophages, higher number of CD11c+ crownlike structures, and decreased vimentin in the AT of patients with active CD compared with controls. PCR revealed no differences in mRNA expression of any analyzed markers in patients with CD. Conclusions: Chronic exposure to GCs due to CD increases the presence of AT macrophages, a hallmark of AT inflammation. Hence, AT inflammation may be the source of the systemic inflammation seen in CD, which in turn may contribute to obesity, insulin resistance, and cardiovascular disease in these patients.

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DO - https://doi.org/10.1210/jc.2018-02552

M3 - Article

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SN - 0021-972X

VL - 104

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EP - 2461

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

IS - 6

ER -

Active Cushing disease is characterized by increased adipose tissue macrophage presence

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