Document Detail


Exposure to in utero lipopolysaccharide induces inflammation in the fetal ovine skin.
MedLine Citation:
PMID:  20923949     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Inflammation is a defensive process by which the body responds to both localized and systemic tissue damage by the induction of innate and adaptive immunity. Literature from human and animal studies links inappropriate in utero inflammation to preterm parturition and fetal injury. The pathways by which such inflammation may cause labor, however, are not fully understood. Any proinflammatory agonist in the amniotic fluid will contact the fetal skin, in its entirety, but a potential role of the fetal skin in the pathways to labor have not previously been explored. We hypothesized that the fetal skin would respond robustly to the presence of intra-amniotic lipopolysaccharide (LPS) in our ovine model of in utero inflammation. In vitro and in utero exposure of fetal ovine keratinocytes or fetal skin to Escherichia coli LPS reliably induced significant increases in interleukin 1β (IL-1β), IL-6, tumor necrosis factor α (TNF-α), and IL-8 expression. We demonstrate that, in utero, this expression requires direct exposure with LPS suggesting that the inflammation is triggered directly in the skin itself, rather than as a secondary response to a systemic stimuli and that inflammation involves Toll-like receptor (TLR) regulation and neutrophil chemotaxis in concordance with an acute inflammatory reaction. We show that this response involves multiple inflammatory mediators, TLR regulation, and localized inflammatory cell influx characteristic of an acute inflammatory reaction. These novel data strongly suggests that the fetal skin acts as an important mediator of the fetal inflammatory response and as such may contribute to preterm birth.
Authors:
Matthew W Kemp; Masatoshi Saito; Ilias Nitsos; Alan H Jobe; Suhas G Kallapur; John P Newnham
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-10-05
Journal Detail:
Title:  Reproductive sciences (Thousand Oaks, Calif.)     Volume:  18     ISSN:  1933-7205     ISO Abbreviation:  Reprod Sci     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2010-12-23     Completed Date:  2011-04-11     Revised Date:  2011-11-29    
Medline Journal Info:
Nlm Unique ID:  101291249     Medline TA:  Reprod Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  88-98     Citation Subset:  IM    
Affiliation:
School of Women's and Infants' Health, The University of Western Australia, Perth, Australia. mkemp@meddent.uwa.edu.au
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MeSH Terms
Descriptor/Qualifier:
Amnion / drug effects
Animals
Cells, Cultured
Dermatitis, Contact / etiology*
Escherichia coli
Female
Fetal Diseases / chemically induced*
Gene Expression
Immunohistochemistry
Interleukin-1 / genetics
Interleukin-1beta / genetics
Interleukin-8 / genetics
Keratinocytes / chemistry,  drug effects,  metabolism
Lipopolysaccharides / administration & dosage*
Polymerase Chain Reaction
Pregnancy
Premature Birth / etiology
RNA, Messenger / analysis
Sheep / embryology*
Skin / chemistry,  drug effects,  embryology*
Toll-Like Receptor 4 / analysis
Tumor Necrosis Factor-alpha / genetics
Grant Support
ID/Acronym/Agency:
HD 57869/HD/NICHD NIH HHS; R01 HD057869-03/HD/NICHD NIH HHS; R01 HD057869-04/HD/NICHD NIH HHS
Chemical
Reg. No./Substance:
0/Interleukin-1; 0/Interleukin-1beta; 0/Interleukin-8; 0/Lipopolysaccharides; 0/RNA, Messenger; 0/Toll-Like Receptor 4; 0/Tumor Necrosis Factor-alpha

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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