Estrogen regulates cytokine production and apoptosis in PMA-differentiated, macrophage-like U937 cells

J Cell Biochem. 2003 Sep 1;90(1):187-96. doi: 10.1002/jcb.10607.


We have investigated the effects of sex steroids, estradiol (E2), and testosterone (T) on the synthesis of tumor necrosis factor alpha (TNF-alpha) and interleukin-10 (IL-10) in phorbol-myristate-acetate (PMA)-differentiated human monoblastic U937 cells. The ability of both hormones to modulate the viability and programmed cell death of macrophage-like PMA-differentiated U937 cells was also inspected. E2 increased TNF-alpha synthesis, whereas T had no effect on the production of this cytokine. The combination of E2 and its antagonist tamoxifen or ICI-182,789 completely abolished the induction of TNF-alpha, while combination of T and its antagonist Casodex (CSDX) did not significantly affect TNF-alpha production by U937 cells. Exposure of cells to E2 resulted in a dose-dependent decrease of IL-10 synthesis, while again T did not show any detectable effect. In addition, E2 induced a significant increase of apoptosis in macrophage-like U937 cells and this increase was inhibited by the simultaneous addition of either tamoxifen or ICI-182. In contrast, T alone or in combination with CSDX did not modify apoptotic rates of U937 cells. This evidence, taken together, suggests that estrogens, but not androgens, exert a pro-inflammatory action through the modulation of TNF-alpha and IL-10, and regulate the immune effector cells by the induction of programmed cell death.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / physiology*
  • Cell Differentiation / physiology
  • Cell Survival
  • Estrogens / metabolism*
  • Humans
  • Interleukin-10 / metabolism*
  • Macrophages / cytology
  • Macrophages / physiology*
  • Receptors, Androgen / metabolism
  • Receptors, Estrogen / metabolism
  • Testosterone / metabolism*
  • Tetradecanoylphorbol Acetate / metabolism*
  • Tumor Necrosis Factor-alpha / metabolism*
  • U937 Cells


  • Estrogens
  • Receptors, Androgen
  • Receptors, Estrogen
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Testosterone
  • Tetradecanoylphorbol Acetate