LEIMGRUBER CAROLINA
Congresos y reuniones científicas
Título:
Testosterone modulates prostate smooth muscle cell response to bacterial LPS
Autor/es:
LEIMGRUBER C; QUINTAR AA; MALDONADO CA
Lugar:
Río Janeiro
Reunión:
Congreso; 10th International Congress on Cell Biology (ICCB); 2012
Resumen:
Prostate smooth muscle cells(pSMCs) play a key role in prostate physiology regulated by Testosterone. We previously demonstrated that LPS induces dedifferentiation and proinflammatory response of pSMCs. Our aim was to elucidate a possible modulation of pSMC response to LPS by Testosterone. Rat pSMCs were treated in vitro with LPS (1 or 10 µg/ml) for 24 or 48h with or without Testosterone(10-7M). Ultraestructural examination showed well-developed proteinopoietic organelles and loss of the contractile apparatus after LPS. Meanwhile, pSMCs conserved a more-differentiated phenotype with Testosterone. Furthermore, LPS challenge decreased ACTA2 filaments and calponin expression (p<0,01vsunstimulated) in a dose- and time-dependent manner as assessed by inmunofluorescence and western blot. Moreover, after LPS pSMCs expressed vimentin, a fibroblast marker. Interestingly, Testosterone abrogated LPS-induced changes, being only detectable after 10ug/ml of LPS for 48h (p<0,05vsLPS without Testosterone). LPS also incited an increase in TLR4 signal (LPS receptor) (p<0,001vsunstimulated) and in TNF-α and IL6 (ELISA) secretion by pSMCs; both effects were reduced by Testosterone (IL6 p<0,01vsLPS without Testosterone; TNFα p<0,05vsLPS without Testosterone). Finally, nuclear NF-кB translocation was analyzed by fluorescence as a parameter of TLR4 activation. A peak of 21% of pSMCs with nuclear NF-кB was observed at 15 min after LPS, compared to the 7,5% of positive cells with Testosterone. These results demonstrate that Testosterone regulates pSMCs response to LPS, leading to a reduction of proinflammatory mediators and the maintenance of a differentiated phenotype, which reinforce the homeostatic role of androgens into the prostate.