Dehydroepiandrosterone induces the transforming growth factor-beta production by murine macrophages.
Dehydroepiandrosterone(DHEA), a predominant androgen secreted by the adrenal cortex, and dehydroepiandrosterone sulfate (DHEAS). Its predominant form in serum, were investigated for their role in the regulation of transforming growth factor-beta (TGF beta) production by murine macrophages. Using a bioassay based on the growing inhibition to Mv-1-Lu cells and RT-PCR analysis, the effect of DHEA and DHEAS on the TGF-beta production and gene expression was studied. Results suggested that DHEA at relatively high concentration (10 microM) significantly induced TGF-beta secretion by both peritoneal cells and P388D1 macrophage-like cells. For the cells treated with DHEAS, no significant increase in TGF-beta secretion was found statistically. Result of RT-PCR confirmed the observation that cDNA from the cells pretreated with DHEA generated a significant amount of amplicons but cDNA samples obtained from both control cells and DHEAS-treated cells showed relatively weak signals. In a quantitative RT-PCR analysis, both DHEAS-treated cells and control cells failed to compete with internal standards and failed to produce any detectable amplicons. Dexamethasone, one of the commonly used glucocorticoids, induced an increase in TGF-beta secretion and in mRNA level. Dexamethasone and DHEA failed to show a synergistic effect on the DHEA-induced increase in TGF-beta secretion and gene expression. The biological significance for DHEA to act as a positive stimulator for TGF-beta production and its role in glucocorticoid-mediated immunoregulation needs to be further delineated.
Wu
M F
MF
Department of Biology, National Taiwan Normal University, Taipei.
Chang
H L
HL
Tseng
J
J
D000818:Animals; D002478:Cells, Cultured; D003687:Dehydroepiandrosterone / Q000494:pharmacology*; D019314:Dehydroepiandrosterone Sulfate / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004347:Drug Interactions; D005938:Glucocorticoids / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*
D005938:Glucocorticoids; D016212:Transforming Growth Factor beta; D003687:Dehydroepiandrosterone; D019314:Dehydroepiandrosterone Sulfate; D003907:Dexamethasone