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Open AccessArticle

Omega-3 Fatty Acid-Derived Resolvin D2 Regulates Human Placental Vascular Smooth Muscle and Extravillous Trophoblast Activities

1
Division of Biomedical Sciences, School of Medicine, University of California, Riverside, Riverside, CA 92521, USA
2
Department of Nutrition & Health Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, USA
3
Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198, USA
4
Cytotechnology Education, College of Allied Health Professions, University of Nebraska Medical Center, Omaha, NE 68198, USA
5
Pediatrics Department, University of Nebraska Medical Center, Omaha, NE 68198, USA
6
Medical Nutrition Education, College of Allied Health Professions, University of Nebraska Medical Center, Omaha, NE 68198, USA
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(18), 4402; https://doi.org/10.3390/ijms20184402
Received: 31 July 2019 / Revised: 30 August 2019 / Accepted: 4 September 2019 / Published: 7 September 2019
(This article belongs to the Special Issue Omega-3 Fatty Acids in Health and Disease: New Knowledge 2019)
Omega-3 fatty acids are important to pregnancy and neonatal development and health. One mechanism by which omega-3 fatty acids exert their protective effects is through serving as substrates for the generation of specialized pro-resolving lipid mediators (SPM) that potently limit and resolve inflammatory processes. We recently identified that SPM levels are increased in maternal blood at delivery as compared to umbilical cord blood, suggesting the placenta as a potential site of action for maternal SPM. To explore this hypothesis, we obtained human placental samples and stained for the SPM resolvin D2 (RvD2) receptor GPR18 via immunohistochemistry. In so doing, we identified GPR18 expression in placental vascular smooth muscle and extravillous trophoblasts of the placental tissues. Using in vitro culturing, we confirmed expression of GPR18 in these cell types and further identified that stimulation with RvD2 led to significantly altered responsiveness (cytoskeletal changes and pro-inflammatory cytokine production) to lipopolysaccharide inflammatory stimulation in human umbilical artery smooth muscle cells and placental trophoblasts. Taken together, these findings establish a role for SPM actions in human placental tissue. View Full-Text
Keywords: omega-3 fatty acids; specialized pro-resolving mediators; placenta; Resolvin D2; delivery; GPR18; trophoblasts; inflammation omega-3 fatty acids; specialized pro-resolving mediators; placenta; Resolvin D2; delivery; GPR18; trophoblasts; inflammation
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Ulu, A.; Sahoo, P.K.; Yuil-Valdes, A.G.; Mukherjee, M.; Van Ormer, M.; Muthuraj, P.G.; Thompson, M.; Anderson Berry, A.; Hanson, C.K.; Natarajan, S.K.; Nordgren, T.M. Omega-3 Fatty Acid-Derived Resolvin D2 Regulates Human Placental Vascular Smooth Muscle and Extravillous Trophoblast Activities. Int. J. Mol. Sci. 2019, 20, 4402.

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