Omega-3 Polyunsaturated Fatty Acids Reduce Preterm Labor by Inhibiting Trophoblast Cathepsin S and Inflammasome Activation

In this study, we found that inflammasome-related molecules and IL-1β in trophoblasts were activated by TNF-α derived from lipopolysaccharide-stimulated THP-1 cell-conditioned medium and recombinant TNF-α protein. The results demonstrated that stimulation with TNF-α caused lysosomal rupture in trophoblasts, which accelerated cathepsin S diffusion from lysosomes to the cytosol and activated NLRP1 and AIM2 inflammasomes, thereby increasing IL-1β secretion. Moreover, in response to LPS challenge, TNF-α increased trophoblast cell death and decreased cell viability through inflammasome and cathepsin S activation. Stearidonic acid (SDA; 18:4n-3) and docosahexaenoic acid (DHA; 22:6n-3) inhibited inflammasome-related molecule synthesis and cathepsin S and caspase-1 activation, which further reduced the preterm delivery rate of pregnant mice induced by lipopolysaccharide (92.9% vs 69.7% [DHA]; 92.9% vs 53.5% [SDA]). Higher expression of TNF-α, IL-1β, prostaglandin E2, and cathepsin S, but lower resolvin D1 expression, was observed in preterm pregnant mice than in controls. Similarly, resolvin D1 was highly expressed in women with term delivery compared with women with preterm delivery. Thus, SDA and DHA may attenuate macrophage-derived TNF-α inducing cathepsin S and inflammasome activation, IL-1β secretion and placental trophoblast cell death. These functions are implicated in the preventive effects of SDA and DHA on preterm labo...

Source: Clinical Science - October 4, 2018 Category: Biomedical Science Authors: Chen, C. Y., Chen, C.-Y., Liu, C.-C., Chen, C.-P. Tags: PublishAheadOfPrint Source Type: research