Estrogen regulates cytokine production and apoptosis in PMA-differentiated, macrophage-like U937 cells.
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.
Carruba
Giuseppe
G
Department of Experimental Oncology and Clinical Application, University of Palermo, Palermo, Italy. lucashbl@unipa.it
D'Agostino
Pietro
P
Miele
Monica
M
Calabrò
Maurizio
M
Barbera
Caterina
C
Bella
Gloria Di
GD
Milano
Salvatore
S
Ferlazzo
Viviana
V
Caruso
Rosalba
R
Rosa
Marzia La
ML
Cocciadiferro
Letizia
L
Campisi
Ildegarda
I
Castagnetta
Luigi
L
Cillari
Enrico
E
D017209:Apoptosis / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D002470:Cell Survival; D004967:Estrogens / Q000378:metabolism*; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism*; D008264:Macrophages / Q000166:cytology / Q000502:physiology*; D011944:Receptors, Androgen / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D013739:Testosterone / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D020298:U937 Cells
D004967:Estrogens; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D013739:Testosterone; D013755:Tetradecanoylphorbol Acetate