Details

Autor(en) / Beteiligte

• Masquelier, Julien
• Alhouayek, Mireille
• Terrasi, Romano
• Bottemanne, Pauline
• Paquot, Adrien
• Muccioli, Giulio G.

Titel

Lysophosphatidylinositols in inflammation and macrophage activation: Altered levels and anti-inflammatory effects

Ist Teil von

• Biochimica et biophysica acta. Molecular and cell biology of lipids, 2018-12, Vol.1863 (12), p.1458-1468

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2018

Quelle

Elsevier ScienceDirect Journals

Beschreibungen/Notizen

• Lysophosphatidylinositols (LPI) are bioactive lipids that are implicated in several pathophysiological processes such as cell proliferation, migration and tumorigenesis and were shown to play a role in obesity and metabolic disorders. Often, these effects of LPI were due to activation of the G protein-coupled receptor GPR55. However, the role of LPI and GPR55 in inflammation and macrophage activation remains unclear. Therefore, we thought to study the effect of macrophage activation and inflammation on LPI levels and metabolism. To do so, we used J774 and BV2 cells in culture activated with lipopolysaccharides (LPS, 100 ng/mL) as well as primary mouse alveolar and peritoneal macrophages. We also quantified LPI levels in the cerebellum, lung, liver, spleen and colon of mice with a systemic inflammation induced by LPS (300 μg/kg) and in the colon of mice with acute colitis induced by dextran sulfate sodium (DSS) or trinitrobenzene sulfonic acid (TNBS) and chronic DSS-induced colitis. Our data show that LPS-induced macrophage activation leads to altered LPI levels in both the cells and culture medium. We also show that cytosolic phospholipase A2α (cPLA2α) and α/β‑hydrolase domain 6 (ABHD6) are among the enzymes implicated in LPI metabolism in J774 macrophages. Indeed, ABHD6 and cPLA2α inhibition increased 20:4-LPI levels in LPS-activated macrophages. Furthermore, incubation of LPS-activated cells with LPI decreased J774 activation in a GPR55-dependent manner. In vivo, LPI levels were altered by inflammation in the liver, spleen and colon. These alterations are tissue dependent and could highlight a potential role for LPI in inflammatory processes. •Lysophosphatidylinositols are the endogenous ligands of the GPR55 receptor.•Lysophosphatidylinositol levels are altered by macrophage activation and inflammation.•ABHD6 and cPLA2α are implicated in lysophosphatidylinositol metabolism in macrophages.•Lysophosphatidylinositol levels are decreased in acute and chronic models of colitis.