Glibenclamide inhibits NLRP3 inflammasome-mediated IL-1β secretion in human trophoblasts

Infection-associated pregnancy complications cause premature delivery. caspase-1 is involved in the maturation of interleukin (il)-1β,which is activated by the nlrp3 inflammasome. to characterize the significance of the nlrp3 inflammasome pathway in the placenta,the effects of activators and inhibitors on nlrp3-related molecules were examined using isolated primary trophoblasts. caspase-1 and il-1β mrna expression was markedly increased in response to lipopolysaccharide (lps),a toll-like receptor (tlr)4 ligand. treatment with the potassium ionophore nigericin significantly increased the level of activated caspase-1. treatment with either lps or nigericin stimulated il-1β secretion,whereas pretreatment with the atp-sensitive k+ channel inhibitor glibenclamide,the rho-associated coiled-coil kinase inhibitor y-27632,or a caspase-1 inhibitor significantly decreased nigericin-induced il-1β secretion. in addition,dibutyryl-camp,which induces trophoblast differentiation,decreased expression of nlrp3,caspase-1,and il-1β. these findings suggest that trophoblasts can secrete il-1β through the nlrp3/caspase-1 pathway,which is suppressed by glibenclamide,and that the tlr4-mediated nlrp3 inflammasome pathway is more likely to be stimulated in undifferentiated than differentiated trophoblasts. our data support the hypothesis that inhibition of the nlrp3 inflammasome can suppress placental inflammation-associated disorders. © 2017 the authors