Resolvin D1 reduces inflammation in co-cultures of primary human macrophages and adipocytes by triggering macrophages. (November 2021)

• Record Type: Journal Article
• Authors: Gemperle, Claudio; Tran, Syndi; Schmid, Mattia; Rimann, Nicole; Marti-Jaun, Jacqueline; Hartling, Ivan; Wawrzyniak, Paulina; Hersberger, Martin
• Is Part Of: Prostaglandins, leukotrienes, and essential fatty acids. Volume 174(2021)
• Publication Date: 2021-11
• Subjects: Specialized pro-resolving mediators -- Adipose tissue inflammation -- Resolvin D1 -- Co-culture -- Mesenchymal stem cells -- Primary human macrophages; Lipids -- Periodicals; Unsaturated fatty acids -- Periodicals; Prostaglandins -- Periodicals; Leukotrienes -- Periodicals; Fatty Acids, Unsaturated -- Periodicals; Acides gras insaturés -- Périodiques; Prostaglandines -- Périodiques; Leucotriènes -- Périodiques; Lipides -- Périodiques; 612.01577
• DOI: 10.1016/j.plefa.2021.102363
• Languages: English
• ISSNs: 0952-3278

Abstract

Highlights: Resolvin D1 reduces pro-inflammatory adipokine secretion in a co-culture system of primary human macrophages and mesenchymal stem cell derived human adipocytes. Resolvin D1 reduces the secretion of pro-inflammatory adipokines in primary human macrophages. Resolvin D1 has no effect on the secretion of adipokines from mesenchymal stem cell derived human adipocytes. This suggests that resolvin D1 triggers primary human macrophages but not human adipocytes to reduce adipose tissue inflammation. Abstract: Obesity leads to chronic inflammation of the adipose tissue which is tightly associated with the metabolic syndrome, type 2 diabetes and cardiovascular disease. Inflammation of the adipose tissue is mainly characterized by the presence of crown-like structures composed of inflammatory macrophages in the neighborhood of adipocytes. Resolvin D1 (RvD1), a potent anti-inflammatory and pro-resolving lipid mediator derived from the omega-3 fatty acid docosahexaenoic acid, has been shown to reduce the inflammatory tone of adipose tissue in animal models but the underlying mechanism is not clear. We investigated the effect of RvD1 on the inflammatory state of a human co-culture system of adipocytes and macrophages. For this, human mesenchymal stem cells were differentiated into mature adipocytes and overlaid with human primary macrophages. In this co-culture, 10–500 nM RvD1 dose-dependently reduced the secretion of the pro-inflammatory cytokine IL-6 (-21%) and its soluble receptor IL-6Rα (-22%), of the chemokine MCP-1 (-13%), and of the adipokine leptin (-22%). Similarly, we observed a reduction in secretion of the soluble receptor IL-6Rα (-20%), and TNF-α (-11%) when macrophages alone were treated with RvD1, while no change of cytokine secretion was observed when adipocytes were treated with RvD1. We conclude that RvD1 polarizes macrophages to an anti-inflammatory phenotype, which in turn modulates inflammation in adipocytes.