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, b ut in obesity, adipose tissue hypertrophy persists despite increased TNF al pha 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 g ene expression in human adipocytes and preadipocytes. Using RT multiplex PC R, the expression of the proapoptotic genes interleukin-1 beta (IL-1 beta)- converting enzyme (ICE) and TNF alpha and the antiapoptotic genes bcl-2, nu clear factor-kappaB (NF kappaB), and NF kappaB inhibitory subunit, I kappaB , were examined. The expression and release of IL-1 beta, a postulated down stream effector of ICE-mediated apoptosis, were also determined. TNF alpha increased the messenger ribonucleic acid levels of ICE, TNF alpha, IL-1 bet a, bcl-2, and NF kappaB in preadipocytes and adipocytes (P < 0.01). Dex inh ibited TNF<alpha>-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 alp ha was reduced to control levels (P < 0.01) by Dex. Insulin had no signific ant effect on TNF<alpha>-induced apoptosis and gene expression. In obesity, glucocorticoids may reduce TNF alpha actions in adipose tissue by inhibiti ng TNF alpha -induced apoptosis, IL-1 beta release, and TNF alpha expressio n.