Nitric oxide mediates prostaglandins' deleterious effect on lipopolysaccharide-triggered murine fetal resorption

被引:55
作者
Aisemberg, J.
Vercelli, C.
Billi, S.
Ribeiro, M. L.
Ogando, D.
Meiss, R.
McCann, S. M.
Rettori, V.
Franchi, A. M.
机构
[1] Univ Buenos Aires, Ctr Estudiso Farmacol & Bot, Natl Res Council, Lab Physiopathol Pregnancy, Buenos Aires, DF, Argentina
[2] Univ Buenos Aires, Ctr Estudiso Farmacol & Bot, Natl Res Council, Lab Neuroendocrinol, Buenos Aires, DF, Argentina
[3] Natl Acad Med, Inst Canc Res, Buenos Aires, DF, Argentina
关键词
embryonic resorption; uteri; decidua; peroxynitrite; sepsis;
D O I
10.1073/pnas.0702279104
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Genital tract bacterial infections could induce abortion and are some of the most common complications of pregnancy; however, the mechanisms remain unclear. We investigated the role of prostaglandins (PGs) in the mechanism of bacterial lipopolysaccharide (LPS)induced pregnancy loss in a mouse model, and we hypothesized that PGs might play a central role in this action. LPS increased PG production in the uterus and decidua from early pregnant mice and stimulated cyclooxygenase (COX)-11 mRNA and protein expression in the decidua but not in the uterus. We also observed that COX inhibitors prevented embryonic resorption (ER). To study the possible interaction between nitric oxide (NO) and PGs, we administered aminoguanidine, an inducible NO synthase inhibitor. NO inhibited basal PGE and PGF(2 alpha). production in the decidua but activated their uterine synthesis and COX-11 mRNA expression under septic conditions. A NO donor (S-nitroso-N-acetylpenicillamine) produced 100% ER and increased PG levels in the uterus and decidua. LPS-stimulated protein nitration was higher in the uterus than in the decidua. Quercetin, a peroxynitrite scavenger, did not reverse LPS-induced ER. Our results suggest that in a model of septic abortion characterized by increased PG levels, NO might nitrate and thus inhibit COX catalytic activity. ER prevention by COX inhibitors adds a possible clinical application to early pregnancy complications due to infections.
引用
收藏
页码:7534 / 7539
页数:6
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