Inflammasome activation during spontaneous preterm labor with intra-amniotic infection or sterile intra-amniotic inflammation

被引:70
|
作者
Gomez-Lopez, Nardhy [1 ,2 ,3 ,4 ]
Romero, Roberto [1 ,2 ,5 ,6 ,7 ]
Panaitescu, Bogdan [1 ,2 ,3 ]
Leng, Yaozhu [1 ,2 ,3 ]
Xu, Yi [1 ,2 ,3 ]
Tarca, Adi L. [1 ,2 ,3 ]
Faro, Jonathan [1 ,2 ,3 ]
Pacora, Percy [1 ,2 ,3 ]
Hassan, Sonia S. [1 ,2 ,3 ,8 ]
Hsu, Chaur-Dong [3 ]
机构
[1] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, Div Obstet & Maternal Fetal Med, Div Intramural Res,NIH,US Dept HHS, Bethesda, MD USA
[2] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, Div Obstet & Maternal Fetal Med, Div Intramural Res,NIH,US Dept HHS, Detroit, MI USA
[3] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA
[4] Wayne State Univ, Sch Med, Dept Immunol Microbiol & Biochem, Detroit, MI USA
[5] Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA
[6] Michigan State Univ, Dept Epidemiol & Biostat, E Lansing, MI USA
[7] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA
[8] Wayne State Univ, Sch Med, Dept Physiol, Detroit, MI 48201 USA
关键词
MOLECULAR-PATTERN MOLECULES; INTRA-AMNIOTIC INFECTION; GAMMA-INDUCING FACTOR; FOR-GESTATIONAL-AGE; CLINICAL CHORIOAMNIONITIS; MICROBIAL INVASION; CASPASE-1; ACTIVATION; NLRP3; INFLAMMASOME; NALP3; PREMATURE RUPTURE;
D O I
10.1111/aji.13049
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Problem: The inflammasome is implicated in the mechanisms that lead to spontaneous preterm labor (PTL). However, whether there is inflammasome activation in the amniotic cavity of women with PTL and intra-amniotic infection (IAI) or sterile intra-amniotic inflammation (SIAI) is unknown. Method of study: Amniotic fluid samples were collected from women with PTL who delivered at term (n = 31) or preterm without IAI or SIAI (n = 35), with SIAI (n = 27), or with IAI (n = 17). As a readout of inflammasome activation, extracellular ASC (apoptosis-associated speck-like protein containing a CARD) was measured in amniotic fluid by ELISA and the expression of ASC, caspase-1, and interleukin (IL)-1 beta was detected in the chorioamniotic membranes by multiplex immunofluorescence. Acute inflammatory responses in amniotic fluid and the placenta were also evaluated. Results: (a) Amniotic fluid concentrations of ASC and IL-6 were higher in women with PTL and IAI or SIAI than in those who delivered preterm or at term without intra-amniotic inflammation; (b) amniotic fluid concentrations of ASC and IL-6 were lower in women with PTL and SIAI than in those with IAI; (c) there was a significant nonlinear correlation between ASC and IL-6 amniotic fluid concentrations; (d) the expression of inflammasome-related proteins (ASC, caspase-1, and IL-1 beta) in the chorioamniotic membranes was increased in women with PTL and IAI or SIAI than in those who delivered preterm or at term without intra-amniotic inflammation; (e) inflammasome activation in the chorioamniotic membranes was weaker in women with PTL and SIAI than in those with IAI; (f) women with PTL and IAI had elevated amniotic fluid white blood cell counts compared to those without this clinical condition; and (g) severe acute placental inflammatory lesions were observed in women with PTL and IAI and in a subset of women with PTL and SIAI. Conclusion: Inflammasome activation occurs in the settings of intra-amniotic infection and sterile intra-amniotic inflammation during spontaneous preterm labor.
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页数:14
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