Pulmonary and systemic expression of monocyte chemotactic proteins in preterm sheep fetuses exposed to lipopolysaccharide-induced chorioamnionitis

Pediatr Res. 2010 Sep;68(3):210-5. doi: 10.1203/PDR.0b013e3181e9c556.


Monocyte chemoattractant proteins (MCP-1 and MCP-2) mediate monocyte and T-lymphocyte chemotaxis, and IL-1 contributes to the pathogenesis of chorioamnionitis-induced lung inflammation and fetal inflammatory responses. We tested the hypothesis that IL-1 mediates the systemic and pulmonary induction of MCP-1 and MCP-2 in response to lipopolysaccharide (LPS)-induced chorioamnionitis. MCP-1 mRNA, MCP-2 mRNA, and MCP-1 protein expression were measured in two models: 1) intra-amniotic LPS and 2) intra-amniotic recombinant sheep IL-1alpha given at varying intervals before preterm delivery at 124 d GA. Intra-amniotic LPS or IL-1alpha induced MCP-1 mRNA and protein and MCP-2 mRNA in fetal lung many fold at 1-2 d. LPS induced intense MCP-1 expression in subepithelial mesenchymal cells and interstitial inflammatory cells in the lung. Inhibition of IL-1 signaling with recombinant human IL-1 receptor antagonist (rhIL-1ra) did not attenuate LPS induced increase in MCP-1 or MCP-2 expression. MCP-1 and MCP-2 were not induced in liver or chorioamnion, but MCP-1 increased in cord plasma. LPS or IL-1 can induce robust expression of MCP-1 or MCP-2 in the fetal lung. LPS induction of MCP-1 is not IL-1 dependent in fetal sheep. MCP-1 and MCP-2 may be significant contributors to fetal inflammation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Analysis of Variance
  • Animals
  • Chemotaxis / physiology*
  • Chorioamnionitis / chemically induced*
  • Chorioamnionitis / metabolism*
  • Extraembryonic Membranes / metabolism
  • Female
  • Fetus / metabolism
  • Gene Expression Regulation / drug effects*
  • Immunohistochemistry
  • In Situ Hybridization
  • Interleukin-1 / metabolism
  • Lipopolysaccharides / toxicity
  • Liver / metabolism
  • Lung / metabolism*
  • Monocyte Chemoattractant Proteins / blood
  • Monocyte Chemoattractant Proteins / metabolism*
  • Pregnancy
  • Premature Birth / metabolism
  • RNA, Messenger / metabolism*
  • Receptors, Interleukin-1 / antagonists & inhibitors
  • Sheep
  • Western Australia


  • Interleukin-1
  • Lipopolysaccharides
  • Monocyte Chemoattractant Proteins
  • RNA, Messenger
  • Receptors, Interleukin-1