title: Dermatitis as a component of the fetal inflammatory response syndrome is associated with activation of Toll-like receptors in epidermal keratinocytes.
abstract: OBJECTIVE
  Microbial invasion of the amniotic cavity (MIAC) elicits a fetal inflammatory response such as funisitis and chorionic vasculitis. However, little is known about the changes of fetal skin during MIAC. Toll-like receptors recognize microbial products and initiate an immune response. The aims of this study were to examine histopathological features of fetal skin exposed to MIAC and to assess the changes in Toll-like receptor (TLR)-2 and TLR-4 expression.
  
  
  RESULTS
  Skin samples were obtained from fetal autopsies (n = 12). The cases were classified according to the presence (n = 8) or absence (n = 4) of acute chorioamnionitis and analysed by immunohistochemistry using a panel of antibodies. Leucocytic infiltrates into the superficial dermis were observed in cases with chorioamnionitis; the majority of inflammatory cells were neutrophils, lymphocytes and histiocytes. TLR-2 immunoreactivity in the skin was stronger in fetuses with chorioamnionitis than in those without this condition. However, immunoreactivity of TLR-4 in the fetal skin was constitutively expressed, regardless of the presence or absence of chorioamnionitis.
  
  
  CONCLUSIONS
  This study demonstrates for the first time that fetal dermatitis can be detected and is part of the fetal inflammatory response syndrome (FIRS). We propose that this 'FIRS-associated fetal dermatitis' is a fetal counterpart of chorioamnionitis.
authors.affiliation: Perinatology Research Branch, National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA.
authors.forename: Y M
authors.initials: YM
authors.lastname: Kim
authors.forename: R
authors.initials: R
authors.lastname: Romero
authors.forename: T
authors.initials: T
authors.lastname: Chaiworapongsa
authors.forename: J
authors.initials: J
authors.lastname: Espinoza
authors.forename: G
authors.initials: G
authors.lastname: Mor
authors.forename: C J
authors.initials: CJ
authors.lastname: Kim
mesh_terms: D000015:Abnormalities, Multiple / Q000378:metabolism* / Q000473:pathology; D000208:Acute Disease; D000328:Adult; D002821:Chorioamnionitis / Q000378:metabolism* / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D003872:Dermatitis / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005865:Gestational Age; D006801:Humans; D007223:Infant; D007226:Infant Mortality; D007231:Infant, Newborn; D015603:Keratinocytes / Q000378:metabolism* / Q000473:pathology; D008297:Male; D011247:Pregnancy; D012867:Skin / Q000196:embryology / Q000473:pathology; D013577:Syndrome; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D051193:Toll-Like Receptors / Q000378:metabolism*
chemical_list: D016207:Cytokines; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors