Elsevier

Placenta

Volume 27, Issue 8, August 2006, Pages 794-798
Placenta

Current topic
The Placenta Cytokine Network and Inflammatory Signals

https://doi.org/10.1016/j.placenta.2005.08.009Get rights and content

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-α is associated with an increased production for markers of inflammation, fibrotic response, vascular remodeling and proteins facilitating lipid storage within the placenta.

Section snippets

Placental cytokines

Cytokines are mainly but not exclusively produced by cells of the immune system, NK-cells and macrophages in response to an external stimulus. In addition, almost all cell types identified in the uteroplacental tissues participate to the cytokine network (review in Ref. [1]). Virtually, all known cytokines have been found to be expressed in the human placenta although their temporal pattern of expression is still incompletely understood (review in Ref. [2]). Cytokines are produced by the

Cytokines, inflammation and energy homeostasis: immune and metabolic interplays

In general, cytokines which are central player of the inflammatory response are secreted by both the immune system and the adipocyte [13], [14]. The interplay between the two systems becomes more evident in pathological situations such as obesity or diabetes. It is believed that the abnormal metabolic environment generates stimuli within the adipose cell to first increase the production of inflammatory cytokines whose gene expression is minimal under physiological situation. The subsequent

Placental cytokine crosstalks and inflammatory signals

Molecular characterization of cytokines and their receptors has revealed their functional pleiotropism and redundancy. A given cytokine may generate various biological effect depending on the cell type or the developmental stage. For example, leptin induces mitogenesis in placental cells and angiogenesis in umbilical vascular endothelial cells [26], [38]. TNF-α limits invasive properties of first trimester placental explants and stimulates apoptosis in term trophoblasts [27], [28], [29].

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