In vitro progesterone modulation on bacterial endotoxin-induced production of IL-1β, TNFα, IL-6, IL-8, IL-10, MIP-1α, and MMP-9 in pre-labor human term placenta

Reproductive Biology and Endocrinology

Research

G. Estrada-Gutierrez¹  A. Flores-Pliego¹  L. Bermejo-Martínez¹  A. Espejel-Nuñez¹  P. Flores-Espinosa¹  Veronica Zaga-Clavellina²  G. Garcia-Ruíz²  E. Preciado-Martínez²  R. Maida-Claros³ 

[1] Inmunobiochemistry Branch, Instituto Nacional de Perinatología “Isidro Espinosa de los Reyes”, Montes Urales 800, Lomas Virrreyes, 11000, Ciudad de Mexico, Mexico;Inmunobiochemistry Branch, Instituto Nacional de Perinatología “Isidro Espinosa de los Reyes”, Montes Urales 800, Lomas Virrreyes, 11000, Ciudad de Mexico, Mexico;Facultad de Estudios Superiores Cuautitlán, Universidad Nacional Autónoma de México, 54700, Ciudad de Mexico, Estado de Mexico, Mexico;Neonatology Branch, Instituto Nacional de Perinatología “Isidro Espinosa de los Reyes”, Montes Urales 800, Lomas Virreyes, 11000, Ciudad de Mexico, México;

关键词: Progesterone;    Cytokines;    Metalloproteinase;    Bacterial endotoxin;    Inflammation;    Human placenta;    Intrauterine infection;    Preterm labor;   

DOI  :  10.1186/s12958-015-0111-3

 received in 2015-08-18, accepted in 2015-10-02,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundDuring human pregnancy, infection/inflammation represents an important factor that increases the risk of developing preterm labor. The purpose of this study was to determine if pre-treatment with progesterone has an immunomodulatory effect on human placenta production of endotoxin-induced inflammation and degradation of extracellular matrix markers.MethodsPlacentas were obtained under sterile conditions from pregnancies delivered at term before the onset of labor by cesarean section. Explants from central cotyledons of 10 human placentas were pre-treated with different concentrations of progesterone (0.01, 01, 1.0 μM) and then stimulated with 1000 ng/mL of LPS of Escherichia coli. Cytokines TNFα, IL-1β, IL-6, IL-8, MIP-1α, IL-10 concentrations in the culture medium were then measured by specific ELISA. Secretion profile of MMP-9 was evaluated by ELISA and zymogram. Statistical differences were determined by one-way ANOVA followed by the appropriate ad hoc test; P < 0.05 was considered statistically significant.ResultsIn comparison to the explants incubated with vehicle, the LPS treatment led to a significant increase in the level of all cytokines. In comparison to the explants treated only with LPS, pre-treatment with 0.01–1.0 μM progesterone significantly blunted (73, 56, 56, 75, 25, 48 %) the secretion of TNF-α, IL-1β, IL-6, IL-8, MIP-1α, IL-10, respectively. The MMP-9 induced by LPS treatment was inhibited only with the highest concentration of progesterone. Mifepristone (RU486) blocked the immunosuppressive effect of progesterone.ConclusionsThe present results support the concept that progesterone could be part of the compensatory mechanism that limits the inflammation-induced cytotoxic effects associated with an infection process during gestation.

【 授权许可】

CC BY   
© Garcia-Ruíz et al. 2015