title: Intrauterine hypoxia upregulates proinflammatory cytokines and matrix metalloproteinases in fetal guinea pig hearts.
abstract: OBJECTIVE
  Intrauterine infection increases proinflammatory cytokines in the fetus. We hypothesize that proinflammatory cytokines and matrix metalloproteinases (MMPs) are upregulated in fetal hearts in response to hypoxic stress.
  
  
  METHODS
  Timed-pregnant guinea pigs were exposed to either hypoxia (10.5% O(2), 14 day) or normoxia (room air). Left ventricles of fetal hearts were excised from anesthetized age-matched fetuses and frozen until ready for study. Messenger RNA of pro- (TNF-alpha, IL-6, IL-1beta) and anti- (IL-4, TGF, IFN-gamma) inflammatory cytokines and MMP2 and 9 was quantified by real-time PCR, MMP proteins by Western analysis, and MMP activity by gel zymography.
  
  
  RESULTS
  Chronic hypoxia increased (P < .05) TNF-alpha, IL-6, MMP2, and MMP9 mRNA levels but not IL-4, TGF, or IFN-gamma. Hypoxia increased protein levels of MMP9 but not MMP2, despite a hypoxia-induced increase in MMP2 activity.
  
  
  CONCLUSIONS
  Intrauterine hypoxia may be an important stimulus in local generation of selected proinflammatory cytokines and MMPs in fetal hearts.
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors.forename: Chien
authors.initials: C
authors.lastname: Oh
authors.forename: Yafeng
authors.initials: Y
authors.lastname: Dong
authors.forename: Hongshan
authors.initials: H
authors.lastname: Liu
authors.forename: Loren P
authors.initials: LP
authors.lastname: Thompson
mesh_terms: D000818:Animals; D015153:Blotting, Western; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D005311:Fetal Hypoxia / Q000150:complications*; D006168:Guinea Pigs; D006321:Heart / Q000196:embryology*; D007371:Interferon-gamma / Q000096:biosynthesis; D053583:Interleukin-1beta / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D020782:Matrix Metalloproteinases / Q000096:biosynthesis*; D011247:Pregnancy; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015291:Transforming Growth Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D015854:Up-Regulation
chemical_list: D016207:Cytokines; D053583:Interleukin-1beta; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D015291:Transforming Growth Factors; D007371:Interferon-gamma; D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9