Gasdermin D: Evidence of pyroptosis in spontaneous preterm labor with sterile intra-amniotic inflammation or intra-amniotic infection

被引：34

作者：

Gomez-Lopez, Nardhy ^{[1
,2
,3
]}

Romero, Roberto ^{[1
,4
,5
,6
,7
,8
]}

Tarca, Adi L. ^{[1
,2
,9
]}

Miller, Derek ^{[1
,2
]}

Panaitescu, Bogdan ^{[1
,2
]}

Schwenkel, George ^{[1
,2
]}

Gudicha, Dereje W. ^{[1
,2
]}

Hassan, Sonia S. ^{[1
,2
,10
]}

Pacora, Percy ^{[1
,2
]}

Jung, Eunjung ^{[1
,2
]}

Hsu, Chaur-Dong ^{[1
,2
,10
]}

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 Hlth & Human Serv, Detroit, MI USA

[2] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA

[3] Wayne State Univ, Sch Med, Dept Immunol Microbiol & Biochem, Detroit, MI USA

[4] Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA

[5] Michigan State Univ, Dept Epidemiol & Biostat, E Lansing, MI 48824 USA

[6] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI 48201 USA

[7] Detroit Med Ctr, Detroit, MI USA

[8] Florida Int Univ, Dept Obstet & Gynecol, Miami, FL 33199 USA

[9] Wayne State Univ, Dept Comp Sci, Coll Engn, Detroit, MI 48201 USA

[10] Wayne State Univ, Dept Physiol, Sch Med, Detroit, MI 48201 USA

来源：

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY | 2019年 / 82卷 / 06期

基金：

美国国家卫生研究院;

关键词：

amniotic fluid; caspase-1; inflammasome; interleukin-1beta; parturition; pregnancy; BLOOD-CELL COUNT; AMNIOTIC-FLUID INTERLEUKIN-6; MOLECULAR-PATTERN MOLECULES; GAMMA-INDUCING FACTOR; MICROBIAL INVASION; PREMATURE RUPTURE; GRAM STAIN; HISTOLOGIC CHORIOAMNIONITIS; CLINICAL-SIGNIFICANCE; IL-1-BETA RELEASE;

D O I：

10.1111/aji.13184

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 Pyroptosis, inflammatory programmed cell death, is initiated through the inflammasome and relies on the pore-forming actions of the effector molecule gasdermin D. Herein, we investigated whether gasdermin D is detectable in women with spontaneous preterm labor and sterile intra-amniotic inflammation or intra-amniotic infection. Method of study Amniotic fluid samples (n = 124) from women with spontaneous preterm labor were subdivided into the following groups: (a) those who delivered at term (n = 32); and those who delivered preterm (b) without intra-amniotic inflammation (n = 41), (c) with sterile intra-amniotic inflammation (n = 32), or (d) with intra-amniotic infection (n = 19), based on amniotic fluid IL-6 concentrations and the microbiological status of amniotic fluid (culture and PCR/ESI-MS). Gasdermin D concentrations were measured using an ELISA kit. Multiplex immunofluorescence staining was also performed to determine the expression of gasdermin D, caspase-1, and interleukin-1 beta in the chorioamniotic membranes. Flow cytometry was used to detect pyroptosis (active caspase-1) in decidual cells from women with preterm labor and birth. Results (a) Gasdermin D was detected in the amniotic fluid and chorioamniotic membranes from women who underwent spontaneous preterm labor/birth with either sterile intra-amniotic inflammation or intra-amniotic infection, but was rarely detected in those without intra-amniotic inflammation. (b) Amniotic fluid concentrations of gasdermin D were higher in women with intra-amniotic infection than in those with sterile intra-amniotic inflammation, and its expression in the chorioamniotic membranes was associated with caspase-1 and IL-1 beta (inflammasome mediators). (c) Decidual stromal cells and leukocytes isolated from women with preterm labor and birth are capable of undergoing pyroptosis given their expression of active caspase-1. Conclusion Pyroptosis can occur in the context of sterile intra-amniotic inflammation and intra-amniotic infection in patients with spontaneous preterm labor and birth

引用

页数：16

共 174 条

[1] Recent Insights into the Molecular Mechanisms Underlying Pyroptosis and Gasdermin Family Functions [J].