Preterm labor is associated with
inflammation and
infection. The mechanisms underlying the role of
omega-3 fatty acid in
inflammasome activation and prevention of
preterm labor remain unknown. We hypothesized that
omega-3 fatty acid can reduce the rate of
preterm birth induced by
infection and trophoblast
inflammation. In the present study, we found that
inflammasome-related molecules and IL-1β in trophoblasts were activated by TNF-α derived from
lipopolysaccharide (LPS)-stimulated THP-1 cell-
conditioned medium (CM) and recombinant TNF-α
protein. The results demonstrated that stimulation with TNF-α caused lysosomal
rupture in trophoblasts, which accelerated
cathepsin S (CTSS) diffusion from lysosomes to the cytosol and activated NLRP1 (nacht domain-
leucine-rich repeat, and pyd-containing
protein 1) and absent in
melanoma 2 (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 CTSS activation.
Stearidonic acid (SDA; 18:4n-3) and
docosahexaenoic acid (DHA; 22:6n-3) inhibited
inflammasome-related molecule synthesis and CTSS and caspase-1 activation, which further reduced the preterm delivery rate of pregnant mice induced by LPS (92.9 compared with 69.7% (DHA); 92.9 compared with 53.5% (SDA)). Higher expression of TNF-α, IL-1β,
prostaglandin E2, and CTSS, 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 CTSS 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 labor.