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. STUDY DESIGN: 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-1 beta) 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. CONCLUSION: Intrauterine hypoxia may be an important stimulus in local generation of selected proinflammatory cytokines and MMPs in fetal hearts.