Pulmonary and systemic expression of monocyte chemotactic proteins in preterm sheep fetuses exposed to lipopolysaccharide-induced chorioamnionitis.
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.
Shah
Tushar A
TA
Divisions of Neonatology and Pulmonary Biology, Cincinnati Children's Hospital Medical Center, University of Cincinnati, 3333 Burnet Avenue, Cincinnati, OH 45229, USA.
Hillman
Noah H
NH
Nitsos
Ilias
I
Polglase
Graeme R
GR
Pillow
J Jane
JJ
Newnham
John P
JP
Jobe
Alan H
AH
Kallapur
Suhas G
SG
D000704:Analysis of Variance; D000818:Animals; D002633:Chemotaxis / Q000502:physiology*; D002821:Chorioamnionitis / Q000139:chemically induced* / Q000378:metabolism*; D005321:Extraembryonic Membranes / Q000378:metabolism; D005260:Female; D005333:Fetus / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007375:Interleukin-1 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism*; D018945:Monocyte Chemoattractant Proteins / Q000097:blood / Q000378:metabolism*; D011247:Pregnancy; D047928:Premature Birth / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D012756:Sheep; D014904:Western Australia
D007375:Interleukin-1; D008070:Lipopolysaccharides; D018945:Monocyte Chemoattractant Proteins; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1