Abstract
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-1α given at varying intervals before preterm delivery at 124 d GA. Intra-amniotic LPS or IL-1α 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.
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Abbreviations
- BALF:
-
bronchoalveolar lavage fluid
- BPD:
-
bronchopulmonary dysplasia
- IP-10:
-
interferon inducible protein-10 (CXCL10)
- LPS:
-
lipopolysaccharide
- MCP-1:
-
monocyte chemoattractant protein-1 (CCL2)
- MCP-2:
-
monocyte chemoattractant protein-2 (CCL8)
- MIG:
-
monokine-induced by interferon gamma (CXCL9)
- rhIL-1ra:
-
human recombinant interleukin-1 receptor antagonist
- SAA3:
-
serum amyloid-A3
- TLR:
-
Toll-like receptor-4
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Acknowledgements
We thank Angela Keiser, Bill Hull, and Amy Whitescarver for their expert technical assistance.
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Supported by Grants HL-65397 and HD-57869 from the National Institutes of Health.
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Shah, T., Hillman, N., Nitsos, I. et al. Pulmonary and Systemic Expression of Monocyte Chemotactic Proteins in Preterm Sheep Fetuses Exposed to Lipopolysaccharide-Induced Chorioamnionitis. Pediatr Res 68, 210–215 (2010). https://doi.org/10.1203/PDR.0b013e3181e9c556
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DOI: https://doi.org/10.1203/PDR.0b013e3181e9c556
