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Selective IL-1α exposure to the fetal gut, lung, and chorioamnion/skin causes intestinal inflammatory and developmental changes in fetal sheep.
Nikiforou, Maria; Kemp, Matthew W; van Gorp, Rick H; Saito, Masatoshi; Newnham, John P; Reynaert, Niki L; Janssen, Leon E W; Jobe, Alan H; Kallapur, Suhas G; Kramer, Boris W; Wolfs, Tim G A M.
Afiliación
  • Nikiforou M; School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands.
  • Kemp MW; Department of Pediatrics, Maastricht University Medical Center, Maastricht, The Netherlands.
  • van Gorp RH; School of Women's and Infants' Health, The University of Western Australia, Perth, WA, Australia.
  • Saito M; Department of Pediatrics, Maastricht University Medical Center, Maastricht, The Netherlands.
  • Newnham JP; School of Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands.
  • Reynaert NL; School of Women's and Infants' Health, The University of Western Australia, Perth, WA, Australia.
  • Janssen LE; Division of Perinatal Medicine, Tohoku University Hospital, Sendai, Japan.
  • Jobe AH; School of Women's and Infants' Health, The University of Western Australia, Perth, WA, Australia.
  • Kallapur SG; School for Nutrition and Translational Research in Metabolism, Department of Respiratory Medicine, Maastricht University Medical Center, Maastricht, The Netherlands.
  • Kramer BW; School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands.
  • Wolfs TG; Department of Pediatrics, Maastricht University Medical Center, Maastricht, The Netherlands.
Lab Invest ; 96(1): 69-80, 2016 Jan.
Article en En | MEDLINE | ID: mdl-26501868
Chorioamnionitis, caused by intra-amniotic exposure to bacteria and their toxic components, is associated with fetal gut inflammation and mucosal injury. In a translational ovine model, we have shown that these adverse intestinal outcomes to chorioamnionitis were the combined result of local gut and pulmonary-driven systemic immune responses. Chorioamnionitis-induced gut inflammation and injury was largely prevented by inhibiting interleukin-1 (IL-1) signaling. Therefore, we investigated whether local (gut-derived) IL-1α signaling or systemic IL-1α-driven immune responses (lung or chorioamnion/skin-derived) were sufficient for intestinal inflammation and mucosal injury in the course of chorioamnionitis. Fetal surgery was performed in sheep to isolate the lung, gastrointestinal tract, and chorioamnion/skin, and IL-1α or saline was given into the trachea, stomach, or amniotic cavity 1 or 6 days before preterm delivery. Selective IL-1α exposure to the lung, gut, or chorioamnion/skin increased the CD3+ cell numbers in the fetal gut. Direct IL-1α exposure to the gut impaired intestinal zonula occludens protein-1 expression, induced villus atrophy, changed the expression pattern of intestinal fatty acid-binding protein along the villus, and increased the CD68, IL-1, and TNF-α mRNA levels in the fetal ileum. With lung or chorioamnion/skin exposure to IL-1α, intestinal inflammation was associated with increased numbers of blood leukocytes without induction of intestinal injury or immaturity. We concluded that local IL-1α signaling was required for intestinal inflammation, disturbed gut maturation, and mucosal injury in the context of chorioamnionitis.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Corioamnionitis / Interleucina-1alfa / Feto / Mucosa Intestinal / Pulmón Tipo de estudio: Etiology_studies Límite: Animals / Pregnancy Idioma: En Revista: Lab Invest Año: 2016 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Corioamnionitis / Interleucina-1alfa / Feto / Mucosa Intestinal / Pulmón Tipo de estudio: Etiology_studies Límite: Animals / Pregnancy Idioma: En Revista: Lab Invest Año: 2016 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Estados Unidos