Relationship of Notch Signal, Surfactant Protein A, and Indomethacin in Cervix During Preterm Birth: Mast Cell and Jagged-2 May Be Key in Understanding Infection-mediated Preterm Birth

2021 ◽  
pp. 002215542110616
Author(s):  
Sema Avci ◽  
Nilay Kuscu ◽  
Leyla Kilinc ◽  
Ismail Ustunel
Keyword(s):  
Preterm Birth ◽  
Mast Cells ◽  
Preterm Labor ◽  
Protein A ◽  
Surfactant Protein ◽  
Surfactant Protein A ◽  
Notch Signal ◽  
Close Relationship ◽  
Control Switch ◽  
Prostaglandin Inhibitors

Although it is thought that there is a close relationship between Notch signal and preterm birth, the functioning of this mechanism in the cervix is unknown. The efficacy of surfactants and prostaglandin inhibitors in preterm labor is also still unclear. In this study, 48 female CD-1 mice were distributed to pregnant control (PC), Sham, PBS, indomethacin (2 mg/kg; intraperitoneally), lipopolysaccharides (LPS) (25 μg/100 μl; intrauterine), LPS + IND, and Surfactant Protein A Block (SP-A Block: SP-A B; the anti-SP-A antibody was applied 20 µg/100μl; intrauterine) groups. Tissues were examined by immunohistochemistry, immunofluorescence, and Western blot analysis. LPS administration increased the expression of N1 Dll-1 and Jagged-2 (Jag-2). Although Toll-like receptor (Tlr)-2 significantly increased in the LPS-treated and SP-A-blocked groups, Tlr-4 significantly increased only in the LPS-exposed groups. It was observed that Jag-2 is specifically expressed by mast cells. Overall, this experimental model shows that some protein responses increase throughout the uterus, starting at a specific point on the cervix epithelium. Surfactant Protein A, which we observed to be significantly reduced by LPS, may be associated with the regulation of the epithelial response, especially during preterm delivery due to infection. On the contrary, prostaglandin inhibitors can be considered an option to delay infection-related preterm labor with their dose-dependent effects. Finally, the link between mast cells and Jag-2 could potentially be a control switch for preterm birth:

Surfactant protein A modulates the lipopolysaccharide-induced inflammatory response related to preterm birth

Cytokine ◽  
2011 ◽  
Vol 56 (2) ◽  
pp. 442-449 ◽  
Author(s):  
Annamari Salminen ◽  
Reetta Vuolteenaho ◽  
Reija Paananen ◽  
Marja Ojaniemi ◽  
Mikko Hallman
Keyword(s):  
Preterm Birth ◽  
Inflammatory Response ◽  
Protein A ◽  
Surfactant Protein ◽  
Surfactant Protein A

scholarly journals Surfactant Protein-A (SP-A) Selectively Inhibits Prostaglandin F2α (PGF2α) Production in Term Decidua: Implications for the Onset of Labor

Endocrinology ◽  
2011 ◽  
Vol 152 (3) ◽  
pp. 1194-1194
Author(s):  
Victoria V. Snegovskikh ◽  
Vineet Bhandari ◽  
Jo Rae Wright ◽  
Serkalem Tadesse ◽  
Thomas Morgan ◽  
...  
Keyword(s):  
Preterm Birth ◽  
Inflammatory Mediators ◽  
Stromal Cells ◽  
Protein A ◽  
Prostaglandin F2α ◽  
Surfactant Protein ◽  
Surfactant Protein A ◽  
Nucleotide Polymorphisms ◽  
Rt Pcr ◽  
Single Nucleotide

Abstract Context: Labor is characterized by “decidual activation” with production of inflammatory mediators. Recent data suggest that surfactant protein-A (SP-A) may be critical to the onset of labor in mice. Whether this is also true in humans is unclear. Objectives: The aim was to investigate: 1) the expression of SP-A at the maternal-fetal interface; 2) the effect of SP-A on the production of inflammatory mediators by human decidua; and 3) the association between single nucleotide polymorphisms in maternal SP-A genes and spontaneous preterm birth. Research Design and Methods: In situ expression of SP-A was investigated by immunohistochemistry and quantitative RT-PCR. Term decidual stromal cells were isolated, purified, and treated with/without SP-A (1-100 μg/ml), IL-1β, and/or thrombin. Levels of inflammatory mediators [IL-6, IL-8, TNFα, MMP-3, MCP-1, IL-1β, PGE2, prostaglandin F2α (PGF2α)] and angiogenic factors (sFlt-1, VEGF) were measured in conditioned supernatant by ELISA and corrected for protein content. The effect of SP-A on eicosanoid gene expression was measured by quantitative RT-PCR. Results: SP-A localized to endometrium/decidua. High-dose SP-A (100 μg/ml) inhibited PGF2α by term decidual stromal cells without affecting the production of other inflammatory mediators, and this effect occurred at a posttranscriptional level. Decidual SP-A expression decreased significantly with labor. Single nucleotide polymorphisms in the SP-A genes do not appear to be associated with preterm birth. Conclusions: SP-A is produced by human endometrium/decidua, where it significantly and selectively inhibits PGF2α production. Its expression decreases with labor. These novel observations suggest that decidual SP-A likely plays a critical role in regulating prostaglandin production within the uterus, culminating at term in decidual activation and the onset of labor.

Surfactant protein A (SP-A) and SP-A-derived peptide attenuate chemotaxis of mast cells induced by human β-defensin 3

2017 ◽  
Vol 485 (1) ◽  
pp. 107-112
Author(s):  
Yasuaki Uehara ◽  
Motoko Takahashi ◽  
Masaki Murata ◽  
Atsushi Saito ◽  
Rina Takamiya ◽  
...  
Keyword(s):  
Mast Cells ◽  
Protein A ◽  
Surfactant Protein ◽  
Surfactant Protein A

scholarly journals Surfactant protein A suppresses preterm delivery induced by live Escherichia coli in mice†

2018 ◽  
Vol 99 (3) ◽  
pp. 546-555
Author(s):  
Varkha Agrawal ◽  
Mukesh K Jaiswal ◽  
Kenneth D Beaman ◽  
Emmet Hirsch
Keyword(s):  
Escherichia Coli ◽  
Preterm Birth ◽  
Bacterial Infection ◽  
Preterm Delivery ◽  
Macrophage Polarization ◽  
Protein A ◽  
Significant Proportion ◽  
Surfactant Protein ◽  
Surfactant Protein A ◽  
Fetal Survival

AbstractPreterm birth accounts for the majority of neonatal morbidity and mortality in the developed world. A significant proportion of cases of spontaneous preterm labor are attributable to infections within gestational tissues. Surfactant protein A (SP-A), a collectin produced in the fetal lung and other tissues, has been shown previously in mice to suppress preterm delivery due to intrauterine (IU) instillation of sterile proinflammatory substances. Here we report a powerful antilabor effect for SP-A after IU infection with live Escherichia coli. SP-A abolished preterm birth (rate reduced from 100% to 0%) when it was administered into the uterus simultaneously with bacterial infection, reducing it by 75% when administered intravenously at the same time as IU bacterial inoculation, and by 48% when administered intravenously 4 h after IU bacterial infection. This effect on preterm delivery was accompanied by a parallel benefit on fetal survival in utero. SP-A had no effect on bacterial growth but reversed several major consequences of infection, including increased production of inflammatory mediators and a shift in macrophage polarization to the M1 phenotype. These findings suggest that exogenous SP-A has potential use to counteract infection-induced labor by reversing its proinflammatory consequences.

scholarly journals Surfactant protein A reduces TLR4 and inflammatory cytokine mRNA levels in neonatal mouse ileum

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lidan Liu ◽  
Chaim Z. Aron ◽  
Cullen M. Grable ◽  
Adrian Robles ◽  
Xiangli Liu ◽  
...  
Keyword(s):  
Proinflammatory Cytokine ◽  
Inflammatory Cytokine ◽  
Protein A ◽  
Surfactant Protein ◽  
Surfactant Protein A ◽  
Mrna Levels ◽  
Wild Type ◽  
Cytokine Mrna ◽  
Protein Levels ◽  
Cytokine Levels

AbstractLevels of intestinal toll-like receptor 4 (TLR4) impact inflammation in the neonatal gastrointestinal tract. While surfactant protein A (SP-A) is known to regulate TLR4 in the lung, it also reduces intestinal damage, TLR4 and inflammation in an experimental model of necrotizing enterocolitis (NEC) in neonatal rats. We hypothesized that SP-A-deficient (SP-A−/−) mice have increased ileal TLR4 and inflammatory cytokine levels compared to wild type mice, impacting intestinal physiology. We found that ileal TLR4 and proinflammatory cytokine levels were significantly higher in infant SP-A−/− mice compared to wild type mice. Gavage of neonatal SP-A−/− mice with purified SP-A reduced ileal TLR4 protein levels. SP-A reduced expression of TLR4 and proinflammatory cytokines in normal human intestinal epithelial cells (FHs74int), suggesting a direct effect. However, incubation of gastrointestinal cell lines with proteasome inhibitors did not abrogate the effect of SP-A on TLR4 protein levels, suggesting that proteasomal degradation is not involved. In a mouse model of experimental NEC, SP-A−/− mice were more susceptible to intestinal stress resembling NEC, while gavage with SP-A significantly decreased ileal damage, TLR4 and proinflammatory cytokine mRNA levels. Our data suggests that SP-A has an extrapulmonary role in the intestinal health of neonatal mice by modulating TLR4 and proinflammatory cytokines mRNA expression in intestinal epithelium.

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