Dexamethasone inhibits tumor necrosis factor-alpha-induced apoptosis and interleukin-1 beta release in human subcutaneous adipocytes and preadipocytes.
Tumor necrosis factor-alpha (TNF alpha) can decrease adipose tissue mass, but in obesity, adipose tissue hypertrophy persists despite increased TNF alpha expression. The hormonal milieu of obesity may antagonize the adipostat effects of TNF alpha. We examined the effects of insulin and the synthetic glucocorticoid, dexamethasone (Dex), on TNF alpha-induced apoptosis and gene expression in human adipocytes and preadipocytes. Using RT multiplex PCR, the expression of the proapoptotic genes interleukin-1 beta (IL-1 beta)-converting enzyme (ICE) and TNF alpha and the antiapoptotic genes bcl-2, nuclear factor-kappa B (NF kappa B), and NF kappa B inhibitory subunit, I kappa B, were examined. The expression and release of IL-1 beta, a postulated downstream effector of ICE-mediated apoptosis, were also determined. TNF alpha increased the messenger ribonucleic acid levels of ICE, TNF alpha, IL-1 beta, bcl-2, and NF kappa B in preadipocytes and adipocytes (P < 0.01). Dex inhibited TNFalpha-induced messenger ribonucleic acid expression of ICE, TNF alpha, and IL-1 beta (P < 0.01), but not that of bcl-2 and NF kappa B. TNF alpha stimulated IL-1 beta release from preadipocytes and adipocytes up to 20-fold, but the effect was abrogated by Dex. Apoptosis induced by TNF alpha was reduced to control levels (P < 0.01) by Dex. Insulin had no significant effect on TNF alpha-induced apoptosis and gene expression. In obesity, glucocorticoids may reduce TNF alpha actions in adipose tissue by inhibiting TNF alpha-induced apoptosis, IL-1 beta release, and TNF alpha expression.
Zhang
H H
HH
Division of Medical Sciences, University of Birmingham, Birmingham, United Kingdom B15 2TT.
Kumar
S
S
Barnett
A H
AH
Eggo
M C
MC
D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000187:drug effects*; D020170:Caspase 1 / Q000235:genetics; D002478:Cells, Cultured; D016922:Cellular Senescence; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D007375:Interleukin-1 / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D008875:Middle Aged; D016328:NF-kappa B / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000378:metabolism; D012867:Skin / Q000166:cytology*; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000235:genetics / Q000494:pharmacology*
D005938:Glucocorticoids; D007375:Interleukin-1; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D020170:Caspase 1