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Dexamethasone inhibits tumor necrosis factor-α-induced apoptosis and interleukin-1β release in human subcutaneous adipocytes and preadipocytes1
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Zhang, Hui H., Kumar, Sudhesh , Barnett, Anthony H. and Eggo, Margaret C. (2001) Dexamethasone inhibits tumor necrosis factor-α-induced apoptosis and interleukin-1β release in human subcutaneous adipocytes and preadipocytes1. The Journal of Clinical Endocrinology & Metabolism, Volume 86 (Number 6). pp. 2817-2825. doi:10.1210/jcem.86.6.7579 ISSN 0021-972X.
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Official URL: http://dx.doi.org/10.1210/jcem.86.6.7579
Abstract
Tumor necrosis factor-α (TNFα) can decrease adipose tissue mass, but in obesity, adipose tissue hypertrophy persists despite increased TNFα expression. The hormonal milieu of obesity may antagonize the adipostat effects of TNFα. We examined the effects of insulin and the synthetic glucocorticoid, dexamethasone (Dex), on TNFα-induced apoptosis and gene expression in human adipocytes and preadipocytes. Using RT multiplex PCR, the expression of the proapoptotic genes interleukin-1β (IL-1β)-converting enzyme (ICE) and TNFα and the antiapoptotic genes bcl-2, nuclear factor-κB (NFκB), and NFκB inhibitory subunit, IκB, were examined. The expression and release of IL-1β, a postulated downstream effector of ICE-mediated apoptosis, were also determined. TNFα increased the messenger ribonucleic acid levels of ICE, TNFα, IL-1β, bcl-2, and NFκB in preadipocytes and adipocytes (P < 0.01). Dex inhibited TNFα-induced messenger ribonucleic acid expression of ICE, TNFα, and IL-1β (P < 0.01), but not that of bcl-2 and NFκB. TNFα stimulated IL-1β release from preadipocytes and adipocytes up to 20-fold, but the effect was abrogated by Dex. Apoptosis induced by TNFα was reduced to control levels (P < 0.01) by Dex. Insulin had no significant effect on TNFα-induced apoptosis and gene expression. In obesity, glucocorticoids may reduce TNFα actions in adipose tissue by inhibiting TNFα-induced apoptosis, IL-1β release, and TNFα expression.
Item Type: | Journal Article |
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Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
Journal or Publication Title: | The Journal of Clinical Endocrinology & Metabolism |
Publisher: | The Endocrine Society |
ISSN: | 0021-972X |
Official Date: | 2001 |
Volume: | Volume 86 |
Number: | Number 6 |
Page Range: | pp. 2817-2825 |
DOI: | 10.1210/jcem.86.6.7579 |
Status: | Peer Reviewed |
Publication Status: | Published |
Access rights to Published version: | Restricted or Subscription Access |
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