Human prostate epithelial cells can act as early sensors of infection by constitutively expressing TLR4 and up-regulating proinflammatory mediators upon LPS stimulation

GATTI G, ANDREANI V, RIVERO VE, MACCIONI M

Rio de Janeiro, Brasil

Congreso; 13th International Congress in Immunology; 2007

IUIS

Whereas an eruption of information regarding the role of Toll like receptor 4 (TLR4), in activating macrophages and dendritic cells has emerged, very little is known about the role of TLR4 present on epithelial cells from sterile environments, like the prostate. Previous work done in our laboratory has shown that a rat prostate epithelial cell (PECs) line or rat primary PECs constitutively express significant levels of TLR4 and CD14 although not at the cell surface, but intracellularly. However, they are able to respond to lipopolysaccharide (LPS), activating NF-êB transcription factor, inducing the expression of iNOS and secreting NO. Evenmore, numerous chemokine genes are up-regulated in this response. To investigate if human PECs were able to respond to LPS in a similar manner, we studied if the DU145 cell line express TLR4 and CD14. We observed that DU145 cells show high expression of CD14 at the cell surface, but TLR4 expression was only detected intracelullarly. By confocal microscopy, we observed that ALEXA 488–LPS was rapidly internalized in DU145 cells, colocalizing with both, TLR4 and CD14, in the paranuclear area 30 min after cell stimulation. DU145 cells were also able to respond to LPS, translocating NF-KB p65 subunit to the nucleus and up-regulating the expression of IL6 and IL1â genes. Our results indicate that human PECs display a susceptible phenotype to LPS, possibly acting as early sensors in infections and opening up new avenues for understanding the role of TLR4 in this organ.