Advanced glycation end products regulate interleukin-1ß production in human placenta.
J Reprod Dev
; 63(4): 401-408, 2017 Aug 19.
Article
em En
| MEDLINE
| ID: mdl-28515391
ABSTRACT
Maternal obesity is a major risk factor for pregnancy complications, causing inflammatory cytokine release in the placenta, including interleukin-1ß (IL-1ß), IL-6, and IL-8. Pregnant women with obesity develop accelerated systemic and placental inflammation with elevated circulating advanced glycation end products (AGEs). IL-1ß is a pivotal inflammatory cytokine associated with obesity and pregnancy complications, and its production is regulated by NLR family pyrin domain-containing 3 (NLRP3) inflammasomes. Here, we investigated whether AGEs are involved in the activation of NLRP3 inflammasomes using human placental tissues and placental cell line. In human placental tissue cultures, AGEs significantly increased IL-1ß secretion, as well as IL-1ß and NLRP3 mRNA expression. In human placental cell culture, although AGE treatment did not stimulate IL-1ß secretion, AGEs significantly increased IL-1ß mRNA expression and intracellular IL-1ß production. After pre-incubation with AGEs, nano-silica treatment (well known as an inflammasome activator) increased IL-1ß secretion in placental cells. However, after pre-incubation with lipopolysaccharide to produce pro-IL-1ß, AGE treatment did not affect IL-1ß secretion in placental cells. These findings suggest that AGEs stimulate pro-IL-1ß production within placental cells, but do not activate inflammasomes to stimulate IL-1ß secretion. Furthermore, using pharmacological inhibitors, we demonstrated that AGE-induced inflammatory cytokines are dependent on MAPK/NF-κB/AP-1 signaling and reactive oxygen species production in placental cells. In conclusion, AGEs regulate pro-IL-1ß production and inflammatory responses, resulting in the activation of NLRP3 inflammasomes in human placenta. These results suggest that AGEs, as an endogenous and sterile danger signal, may contribute to chronic placental cytokine production.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Placenta
/
Produtos Finais de Glicação Avançada
/
Interleucina-1beta
Tipo de estudo:
Risk_factors_studies
Limite:
Female
/
Humans
/
Pregnancy
Idioma:
En
Revista:
J Reprod Dev
Assunto da revista:
MEDICINA REPRODUTIVA
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Japão