Differential activation of mitogen activated protein kinases and nuclear factor-κB in lipopolysaccharide-treated term and preterm amnion cells

Hyun Sook Jung, Bo Hyun Yoon, Jong Kwan Jun, Miha Kim, Young Ah Kim, Chong Jai Kim

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Intrauterine exposure to amniotic sac infection elicits an inflammatory response from the fetus, which is associated with elevated levels of fetal plasma proinflammatory cytokines, i.e. interleukin-6 (IL-6). We have recently demonstrated that the severity of fetal inflammatory response in terms of gestation period is greater in preterm fetuses than in term fetuses. The activation of mitogen activated protein kinases (MAPKs) and nuclear factor kappa B (NF-κB) is known to be associated with up-regulation of proinflammatory cytokine gene expression in many cell types. In the present study, therefore, we studied patterns of MAPK and NF-κB activation following treatment with bacterial lipopolysaccharide (LPS) in amnion cells obtained from placentas of varying gestational ages to assess whether or not MAPKs and NF-κB are differentially regulated during gestation. MAPK phosphorylation was investigated by immunoblot analysis with phosphospecific antibodies. Transient phosphorylations of extracellular signal-regulated kinase (ERK) 1/2 and c-Jun N-terminal kinase (JNK) were observed in LPS-treated amnion cells, with the degree of phosphorylation being more pronounced in preterm cases. The results of NF-κB-dependent reporter gene expression and electrophoretic mobility shift assay (EMSA) of NF-κB were similar to those of ERK 1/2 and JNK activity. To assess whether the results of in vitro observations reflected in vivo results, we further analyzed amniotic fluid and cord blood IL-6 levels in preterm deliveries with placental inflammation. The analysis also revealed a significantly higher level of IL-6 in cases of ≤31 weeks gestation when compared with those of more than 31 weeks (P<0.001). All these findings strongly suggest that there is an inverse relationship between gestational age and fetal inflammatory response during human gestation, and that differences in the intensity of MAPK activation and NF-κB-dependent transcription pathways are elements of the major underlying mechanism.

Original languageEnglish
Pages (from-to)45-52
Number of pages8
JournalVirchows Archiv
Volume447
Issue number1
DOIs
StatePublished - 1 Jul 2005

Fingerprint

Amnion
NF-kappa B
Mitogen-Activated Protein Kinases
Lipopolysaccharides
Interleukin-6
Pregnancy
Fetus
Mitogen-Activated Protein Kinase 3
JNK Mitogen-Activated Protein Kinases
Mitogen-Activated Protein Kinase 1
Phosphorylation
Gestational Age
Phospho-Specific Antibodies
Cytokines
Gene Expression
Electrophoretic Mobility Shift Assay
Amniotic Fluid
Fetal Blood
Reporter Genes
Placenta

Keywords

  • Amnion
  • ERK 12
  • Interleukin-6
  • JNK
  • Lipopolysaccharide
  • NF-κB

Cite this

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title = "Differential activation of mitogen activated protein kinases and nuclear factor-κB in lipopolysaccharide-treated term and preterm amnion cells",
abstract = "Intrauterine exposure to amniotic sac infection elicits an inflammatory response from the fetus, which is associated with elevated levels of fetal plasma proinflammatory cytokines, i.e. interleukin-6 (IL-6). We have recently demonstrated that the severity of fetal inflammatory response in terms of gestation period is greater in preterm fetuses than in term fetuses. The activation of mitogen activated protein kinases (MAPKs) and nuclear factor kappa B (NF-κB) is known to be associated with up-regulation of proinflammatory cytokine gene expression in many cell types. In the present study, therefore, we studied patterns of MAPK and NF-κB activation following treatment with bacterial lipopolysaccharide (LPS) in amnion cells obtained from placentas of varying gestational ages to assess whether or not MAPKs and NF-κB are differentially regulated during gestation. MAPK phosphorylation was investigated by immunoblot analysis with phosphospecific antibodies. Transient phosphorylations of extracellular signal-regulated kinase (ERK) 1/2 and c-Jun N-terminal kinase (JNK) were observed in LPS-treated amnion cells, with the degree of phosphorylation being more pronounced in preterm cases. The results of NF-κB-dependent reporter gene expression and electrophoretic mobility shift assay (EMSA) of NF-κB were similar to those of ERK 1/2 and JNK activity. To assess whether the results of in vitro observations reflected in vivo results, we further analyzed amniotic fluid and cord blood IL-6 levels in preterm deliveries with placental inflammation. The analysis also revealed a significantly higher level of IL-6 in cases of ≤31 weeks gestation when compared with those of more than 31 weeks (P<0.001). All these findings strongly suggest that there is an inverse relationship between gestational age and fetal inflammatory response during human gestation, and that differences in the intensity of MAPK activation and NF-κB-dependent transcription pathways are elements of the major underlying mechanism.",
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Differential activation of mitogen activated protein kinases and nuclear factor-κB in lipopolysaccharide-treated term and preterm amnion cells. / Jung, Hyun Sook; Yoon, Bo Hyun; Jun, Jong Kwan; Kim, Miha; Kim, Young Ah; Kim, Chong Jai.

In: Virchows Archiv, Vol. 447, No. 1, 01.07.2005, p. 45-52.

Research output: Contribution to journalArticle

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