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Schistosoma japonicum soluble egg antigens attenuate invasion in a first trimester human placental trophoblast model.

McDonald EA, Friedman JF, Sharma S, Acosta L, Pond-Tor S, Cheng L, White ES, Kurtis JD - PLoS Negl Trop Dis (2013)

Bottom Line: Exposure of HTR8 cells to SEA resulted in a pro-inflammatory, anti-invasive signature, characterized by increased pro-inflammatory cytokines (IL-6, IL-8, MCP-1) and TIMP-1.These results are supported by increased IL-6 and IL-8 in the culture media of HTR8 cells exposed to plasma from Schistosoma japonica infected pregnant women.Soluble egg antigens found in circulation during schistosome infection increase pro-inflammatory cytokine production and inhibit the mobility and invasive characteristics of the first trimester HTR8/SVneo trophoblast cell line.

View Article: PubMed Central - PubMed

Affiliation: Center for International Health Research, Rhode Island Hospital, Brown University Medical School, Providence, Rhode Island, United States of America.

ABSTRACT

Background: Schistosomiasis affects nearly 40 million women of reproductive age, and is known to elicit a pro-inflammatory signature in the placenta. We have previously shown that antigens from schistosome eggs can elicit pro-inflammatory cytokine production from trophoblast cells specifically; however, the influence of these antigens on other characteristics of trophoblast function, particularly as it pertains to placentation in early gestation, is unknown. We therefore sought to determine the impact of schistosome antigens on key characteristics of first trimester trophoblast cells, including migration and invasion.

Methods: First trimester HTR8/SVneo trophoblast cells were co-cultured with plasma from pregnant women with and without schistosomiasis or schistosome soluble egg antigens (SEA) and measured cytokine, cellular migration, and invasion responses.

Results: Exposure of HTR8 cells to SEA resulted in a pro-inflammatory, anti-invasive signature, characterized by increased pro-inflammatory cytokines (IL-6, IL-8, MCP-1) and TIMP-1. Additionally, these cells displayed 62% decreased migration and 2.7-fold decreased invasion in vitro after treatment with SEA. These results are supported by increased IL-6 and IL-8 in the culture media of HTR8 cells exposed to plasma from Schistosoma japonica infected pregnant women.

Conclusions: Soluble egg antigens found in circulation during schistosome infection increase pro-inflammatory cytokine production and inhibit the mobility and invasive characteristics of the first trimester HTR8/SVneo trophoblast cell line. This is the first study to assess the impact of schistosome soluble egg antigens on the behavior of an extravillous trophoblast model and suggests that schistosomiasis in the pre-pregnancy period may adversely impact placentation and the subsequent health of the mother and newborn.

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SEA inhibits trophoblast migration.HTR8/SVneo cells were grown to confluence before a linear scratch was made through the center of the growth area. Media was then replaced with either serum-free media alone, or serum-free media with SEA (25 µg/ml) for 48 h. Data for each well was analyzed as the percentage of the original denuded area remaining open at each time point. A and B) A well with media alone, at 0 h and 48 h. C and D) An area scratched and treated with SEA has little cell migration into the scratched region 48 h later. E) The percentage of area filled after 48 h in culture is significantly less in those wells exposed to SEA, P<0.01, n = 5 pairs of HTR8 cells cultured +/− SEA.
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pntd-0002253-g004: SEA inhibits trophoblast migration.HTR8/SVneo cells were grown to confluence before a linear scratch was made through the center of the growth area. Media was then replaced with either serum-free media alone, or serum-free media with SEA (25 µg/ml) for 48 h. Data for each well was analyzed as the percentage of the original denuded area remaining open at each time point. A and B) A well with media alone, at 0 h and 48 h. C and D) An area scratched and treated with SEA has little cell migration into the scratched region 48 h later. E) The percentage of area filled after 48 h in culture is significantly less in those wells exposed to SEA, P<0.01, n = 5 pairs of HTR8 cells cultured +/− SEA.

Mentions: Data analysis was performed using JMP v.10 (SAS Institute, Cary, NC). All data were evaluated for normality using the Shapiro-Wilk test. Those experiments for which all data were normally distributed were further evaluated with ANOVA and t-tests, with means ± SEM reported. For data that was not normally distributed, Wilcoxon Signed Rank analyses were performed, with data reported as median ± IQR. Specifically, cytokine production by HTR8 cells was compared between cells exposed to uninfected plasma and those exposed to infected plasma (Figure 1) as well as cells cultured with media alone and media with SEA (Figures 2 and 3). Similarly, HTR8 migration and invasion were compared between cells cultured with media alone and those with SEA addition to the media (Figures 4 and 5). Statistical significance was considered as P<0.05.


Schistosoma japonicum soluble egg antigens attenuate invasion in a first trimester human placental trophoblast model.

McDonald EA, Friedman JF, Sharma S, Acosta L, Pond-Tor S, Cheng L, White ES, Kurtis JD - PLoS Negl Trop Dis (2013)

SEA inhibits trophoblast migration.HTR8/SVneo cells were grown to confluence before a linear scratch was made through the center of the growth area. Media was then replaced with either serum-free media alone, or serum-free media with SEA (25 µg/ml) for 48 h. Data for each well was analyzed as the percentage of the original denuded area remaining open at each time point. A and B) A well with media alone, at 0 h and 48 h. C and D) An area scratched and treated with SEA has little cell migration into the scratched region 48 h later. E) The percentage of area filled after 48 h in culture is significantly less in those wells exposed to SEA, P<0.01, n = 5 pairs of HTR8 cells cultured +/− SEA.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3675010&req=5

pntd-0002253-g004: SEA inhibits trophoblast migration.HTR8/SVneo cells were grown to confluence before a linear scratch was made through the center of the growth area. Media was then replaced with either serum-free media alone, or serum-free media with SEA (25 µg/ml) for 48 h. Data for each well was analyzed as the percentage of the original denuded area remaining open at each time point. A and B) A well with media alone, at 0 h and 48 h. C and D) An area scratched and treated with SEA has little cell migration into the scratched region 48 h later. E) The percentage of area filled after 48 h in culture is significantly less in those wells exposed to SEA, P<0.01, n = 5 pairs of HTR8 cells cultured +/− SEA.
Mentions: Data analysis was performed using JMP v.10 (SAS Institute, Cary, NC). All data were evaluated for normality using the Shapiro-Wilk test. Those experiments for which all data were normally distributed were further evaluated with ANOVA and t-tests, with means ± SEM reported. For data that was not normally distributed, Wilcoxon Signed Rank analyses were performed, with data reported as median ± IQR. Specifically, cytokine production by HTR8 cells was compared between cells exposed to uninfected plasma and those exposed to infected plasma (Figure 1) as well as cells cultured with media alone and media with SEA (Figures 2 and 3). Similarly, HTR8 migration and invasion were compared between cells cultured with media alone and those with SEA addition to the media (Figures 4 and 5). Statistical significance was considered as P<0.05.

Bottom Line: Exposure of HTR8 cells to SEA resulted in a pro-inflammatory, anti-invasive signature, characterized by increased pro-inflammatory cytokines (IL-6, IL-8, MCP-1) and TIMP-1.These results are supported by increased IL-6 and IL-8 in the culture media of HTR8 cells exposed to plasma from Schistosoma japonica infected pregnant women.Soluble egg antigens found in circulation during schistosome infection increase pro-inflammatory cytokine production and inhibit the mobility and invasive characteristics of the first trimester HTR8/SVneo trophoblast cell line.

View Article: PubMed Central - PubMed

Affiliation: Center for International Health Research, Rhode Island Hospital, Brown University Medical School, Providence, Rhode Island, United States of America.

ABSTRACT

Background: Schistosomiasis affects nearly 40 million women of reproductive age, and is known to elicit a pro-inflammatory signature in the placenta. We have previously shown that antigens from schistosome eggs can elicit pro-inflammatory cytokine production from trophoblast cells specifically; however, the influence of these antigens on other characteristics of trophoblast function, particularly as it pertains to placentation in early gestation, is unknown. We therefore sought to determine the impact of schistosome antigens on key characteristics of first trimester trophoblast cells, including migration and invasion.

Methods: First trimester HTR8/SVneo trophoblast cells were co-cultured with plasma from pregnant women with and without schistosomiasis or schistosome soluble egg antigens (SEA) and measured cytokine, cellular migration, and invasion responses.

Results: Exposure of HTR8 cells to SEA resulted in a pro-inflammatory, anti-invasive signature, characterized by increased pro-inflammatory cytokines (IL-6, IL-8, MCP-1) and TIMP-1. Additionally, these cells displayed 62% decreased migration and 2.7-fold decreased invasion in vitro after treatment with SEA. These results are supported by increased IL-6 and IL-8 in the culture media of HTR8 cells exposed to plasma from Schistosoma japonica infected pregnant women.

Conclusions: Soluble egg antigens found in circulation during schistosome infection increase pro-inflammatory cytokine production and inhibit the mobility and invasive characteristics of the first trimester HTR8/SVneo trophoblast cell line. This is the first study to assess the impact of schistosome soluble egg antigens on the behavior of an extravillous trophoblast model and suggests that schistosomiasis in the pre-pregnancy period may adversely impact placentation and the subsequent health of the mother and newborn.

Show MeSH
Related in: MedlinePlus