Chien Oh1, Yafeng Dong, Hongshan Liu, Loren P Thompson. 1. Department of Obstetrics, Gynecology and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
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. 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-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. CONCLUSION: Intrauterine hypoxia may be an important stimulus in local generation of selected proinflammatory cytokines and MMPs in fetal 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-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. CONCLUSION:Intrauterine hypoxia may be an important stimulus in local generation of selected proinflammatory cytokines and MMPs in fetal hearts.
Authors: Yazan M Al-Hasan; LaShauna C Evans; Gerard A Pinkas; Erinne R Dabkowski; William C Stanley; Loren P Thompson Journal: Reprod Sci Date: 2012-08-24 Impact factor: 3.060
Authors: Janna L Morrison; Kimberley J Botting; Jack R T Darby; Anna L David; Rebecca M Dyson; Kathryn L Gatford; Clint Gray; Emilio A Herrera; Jonathan J Hirst; Bona Kim; Karen L Kind; Bernardo J Krause; Stephen G Matthews; Hannah K Palliser; Timothy R H Regnault; Bryan S Richardson; Aya Sasaki; Loren P Thompson; Mary J Berry Journal: J Physiol Date: 2018-05-30 Impact factor: 5.182