Intrauterine hypoxia upregulates proinflammatory cytokines and matrix metalloproteinases in fetal guinea pig hearts.
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.
Oh
Chien
C
Department of Obstetrics, Gynecology and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Dong
Yafeng
Y
Liu
Hongshan
H
Thompson
Loren P
LP
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
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