Figure 5. TNF-α blockade prevents AT1 receptor-mediated damage in human placental villous explants.

Culturing human villous explants with PE-IgG resulted in TNF-α secretion (A). Co-culturing the explants with PE-IgG and losartan (5μM) or 7-aa (1μM) reduced the cytokine level. Apoptosis was increased in explants incubated with AT1-AA and was partially diminished by blocking TNF-α activity as demonstrated by a TUNEL assay (B). Green; TUNEL-positive cells. Blue; DAPI-positive nuclei. 10X. Quantification of TUNEL staining (C) indicates that co-incubation with PE-IgG and an anti-TNF-α agent (5μg/ml) reduces the amount of apoptosis. Secretion of sFlt-1 (D) and sEng (E) were reduced by co-incubation of the autoantibody with an anti-TNF-α antibody. Six different placentas were collected, and from each, n=4 for every variable, total n=24 per variable. *P<0.05 versus NT-IgG. **P<0.05 versus PE-IgG.