<scp>CXCL</scp>10 and <scp>IL</scp>‐6: Markers of two different forms of intra‐amniotic inflammation in preterm labor

Romero, Roberto; Chaemsaithong, Piya; Chaiyasit, Noppadol; Docheva, Nikolina; Dong, Zhong; Kim, Chong Jai; Kim, Yeon Mee; Kim, Jung Sun; Qureshi, Faisal; Jacques, Suzanne M.; Yoon, Bo Hyun; Chaiworapongsa, Tinnakorn; Yeo, Lami; Hassan, Sonia S.; Erez, Offer; Korzeniewski, Steven J.

doi:10.1111/aji.12685

Cited by 62 publications

(38 citation statements)

References 308 publications

(450 reference statements)

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“…12–15,89,105 Women who underwent spontaneous preterm labor with IAI had higher amniotic fluid concentrations of IL-6 than those who delivered preterm or at term without intra-amniotic inflammation [spontaneous preterm labor with IAI: median 97,800 pg/mL (IQR 15,651–134,950 pg/mL) vs. spontaneous preterm labor without intra-amniotic inflammation: median 507 pg/mL (IQR 187.5–934 pg/mL); p<0.001 or vs. spontaneous preterm labor who delivered at term: median 322 pg/mL (IQR 185–455 pg/mL); p<0.001 (Figure 2). Women who underwent spontaneous preterm labor with SIAI also had increased amniotic fluid concentrations of IL-6 compared to those who delivered preterm or at term without intra-amniotic inflammation [spontaneous preterm labor with SIAI: median 11,247 pg/mL (IQR 5,303–23,354 pg/mL) vs. spontaneous preterm labor without intra-amniotic inflammation: median 507 pg/mL (IQR 187.5–934 pg/mL); p<0.001 or vs spontaneous preterm labor who delivered at term: median 322 pg/mL (IQR 185–455 pg/mL); p<0.001] (Figure 2).…”

Section: Resultsmentioning

confidence: 99%

“…In order to correlate the ASC amniotic fluid concentrations with the degree of intra-amniotic inflammation, amniotic fluid concentrations of IL-6 were determined as previously reported. [12][13][14][15]89,105 Women who underwent spontaneous preterm labor with IAI had higher amniotic fluid concentrations of IL-6 than those who delivered preterm or at term without intra-…”

Section: Il-6 Amniotic Fluid Concentration In Women With Spontaneoumentioning

confidence: 99%

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

Gomez‐Lopez

Romero

Panaitescu

et al. 2018

American J Rep Immunol

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Section: Resultsmentioning

confidence: 99%

Section: Il-6 Amniotic Fluid Concentration In Women With Spontaneoumentioning

confidence: 99%

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

Gomez‐Lopez

Romero

Panaitescu

et al. 2018

American J Rep Immunol

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“…CXCL10 (IP-10) is a 77 amino acid, 10kDA protein that belongs to the CXC family of chemokines 84 , and has been shown to have pleiotropic biological activities 23 . CXCL10 is the most potent chemoattractant for cytotoxic CD8 + T cells 85 and elevated levels of CXCL10 in maternal serum, amniotic fluid, and neonatal cord blood have been associated with infection and preterm birth 21,[86][87][88] . In the mouse, it was described ex vivo that the promoter region of the chemokines CXCL9 and CXCLl10 revealed elevated levels of the repressive histone mark H3K27me3 in DSCs versus myometrial cells, which was then confirmed in vivo 26 .…”

Section: Discussionmentioning

confidence: 99%

Human Chorionic Gonadotropin modulates CXCL10 Expression through Histone Methylation in human decidua

Silasi

You

Simpson

et al. 2020

Sci Rep

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the process of implantation, trophoblast invasion and placentation demand continuous adaptation and modifications between the trophoblast (embryonic) and the decidua (maternal). Within the decidua, the maternal immune system undergoes continued changes, as the pregnancy progress, in terms of the cell population, phenotype and production of immune factors, cytokines and chemokines. Human chorionic gonadotropin (hCG) is one of the earliest hormones produced by the blastocyst and has potent immune modulatory effects, especially in relation to T cells. We hypothesized that trophoblastderived hcG modulates the immune population present at the maternal fetal interface by modifying the cytokine profile produced by the stromal/decidual cells. Using in vitro models from decidual samples we demonstrate that hcG inhibits CXCL10 expression by inducing H3K27me3 histone methylation, which binds to Region 4 of the CXCL10 promoter, thereby suppressing its expression. hCG-induced histone methylation is mediated through EZH2, a functional member of the PRC2 complex. Regulation of CXCL10 expression has a major impact on the capacity of endometrial stromal cells to recruit CD8 cells. We demonstrate the existence of a cross talk between the placenta (hCG) and the decidua (CXCL10) in the control of immune cell recruitment. Alterations in this immune regulatory function, such as during infection, will have detrimental effects on the success of the pregnancy. The coordinated balance between the invading trophoblast and a receptive maternal decidua is critical for the success of pregnancy 1,2. The process of implantation, trophoblast invasion and placentation demand continuous adaptation and modifications between the trophoblast (embryonic) and the decidua (maternal) 3-5. Within the decidua, the maternal immune system undergoes continued modifications, as the pregnancy progresses, in terms of the cell population, phenotype and production of immune factors, cytokines and chemokines 6. These adaptation processes are essential for the normal progression of the pregnancy. The decidua, the pregnant uterine endometrium, has long been considered as a supportive environment for the immune cells and the trophoblast present at the implantation site. However, growing evidence suggest that decidual stromal cells (DSCs) may play a more active role in the regulation of differentiation, migration and function of uterine immune cells 7 as well as in the protection against infections 8. Immune cells are a major cellular component of the human and rodents' pregnant uterus, and their specific role has been an area of active research. During the first trimester of the human pregnancy, 70% of the leukocytes found in the decidua are Natural Killer (NK) cells, 20% to 25% are macrophages, and approximately 1.7% are dendritic cells (DCs) 9-11. In addition, the uterine T cell population expands across gestation, and are mostly regulatory in nature 12. The recruitment of immune cells into the uterus is cell specific and their function is locally controlled 7 .

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“…We next investigated whether the detection of microorganisms is associated with the IL-6 inflammatory response in amniotic fluid. The amniotic fluid concentration of IL-6 was used as the diagnostic criteria for intra-amniotic inflammation as previously described [14,[155][156][157][158]. According to amniotic fluid culture and IL-6 concentrations, we classified the patients into four groups: .…”

Section: The Association Between Microbial Detection and Intra-amniotmentioning

confidence: 99%

Microbial burden and inflammasome activation in amniotic fluid of patients with preterm prelabor rupture of membranes

Theis

Romero

Motomura

et al. 2020

Journal of Perinatal Medicine

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Background Intra-amniotic inflammation, which is associated with adverse pregnancy outcomes, can occur in the presence or absence of detectable microorganisms, and involves activation of the inflammasome. Intra-amniotic inflammasome activation has been reported in clinical chorioamnionitis at term and preterm labor with intact membranes, but it has not yet been investigated in women with preterm prelabor rupture of membranes (preterm PROM) in the presence/absence of detectable microorganisms. The aim of this study was to determine whether, among women with preterm PROM, there is an association between detectable microorganisms in amniotic fluid and intra-amniotic inflammation, and whether intra-amniotic inflammasome activation correlates with microbial burden. Methods Amniotic fluids from 59 cases of preterm PROM were examined for the presence/absence of microorganisms through culture and 16S ribosomal RNA (rRNA) gene quantitative real-time polymerase chain reaction (qPCR), and concentrations of interleukin-6 (IL-6) and ASC [apoptosis-associated spec-like protein containing a caspase recruitment domain (CARD)], an indicator of inflammasome activation, were determined. Results qPCR identified more microbe-positive amniotic fluids than culture. Greater than 50% of patients with a negative culture and high IL-6 concentration in amniotic fluid yielded a positive qPCR signal. ASC concentrations were greatest in patients with high qPCR signals and elevated IL-6 concentrations in amniotic fluid (i.e. intra-amniotic infection). ASC concentrations tended to increase in patients without detectable microorganisms but yet with elevated IL-6 concentrations (i.e. sterile intra-amniotic inflammation) compared to those without intra-amniotic inflammation. Conclusion qPCR is a valuable complement to microbiological culture for the detection of microorganisms in the amniotic cavity in women with preterm PROM, and microbial burden is associated with the severity of intra-amniotic inflammatory response, including inflammasome activation.

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CXCL10 and IL‐6: Markers of two different forms of intra‐amniotic inflammation in preterm labor

Cited by 62 publications

References 308 publications

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

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

Human Chorionic Gonadotropin modulates CXCL10 Expression through Histone Methylation in human decidua

Microbial burden and inflammasome activation in amniotic fluid of patients with preterm prelabor rupture of membranes

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