The placenta cytokine network and inflammatory signals.
Throughout its entire lifespan, the placenta is able to produce as well as respond to a variety of inflammatory stimuli. Many signaling molecules and concurrent pathways responsible for the propagation of an inflammatory response have been identified in placental cells. From early developmental stages onward, the secretory activity of placenta cells clearly contributes to increase local as well as systemic levels of cytokines and inflammatory molecules. Two aspects of the progression of an immune response have been particularly investigated: the highly regulated process of invasion and implantation and, the induction of preterm labor associated with infections. With the progression of pregnancy, the physiological role of most placental cytokines is more uncertain. Many placental cytokines are similar to adipose tissue derived cytokines. One possibility is that they contribute to the low grade systemic inflammation developing during the third trimester of pregnancy. The prevalent hypothesis is that activation of some inflammatory pathways is necessary to induce maternal insulin resistance which is required for the progression of normal gestation. As an integrative organ, the placenta may relay or enhance the contribution made by the cells of the adipose tissue and immune system in non-pregnant individuals. In pregnancy complicated with obesity or diabetes mellitus, continuous adverse stimulus is associated with dysregulation of metabolic, vascular and inflammatory pathways supported by increased circulating concentration of inflammatory molecules. It is believed that maternal adipose tissue and placental cells both contribute to the inflammatory situation by releasing common molecules. For example, the accumulation of leptin and TNF-alpha is associated with an increased production for markers of inflammation, fibrotic response, vascular remodeling and proteins facilitating lipid storage within the placenta.
Hauguel-de Mouzon
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Department of Reproductive Biology, Schwartz Center for Metabolism and Nutrition, Case Western Reserve University, Metro Health Medical Center, 2550 Metrohealth Drive, Cleveland, OH 44109, USA. shdemouzon@metrohealth.org
Guerre-Millo
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M
D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D003920:Diabetes Mellitus / Q000276:immunology; D005260:Female; D006706:Homeostasis / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D009765:Obesity / Q000276:immunology; D010920:Placenta / Q000276:immunology*; D011247:Pregnancy
D016207:Cytokines