The endocannabinoid-derived prostaglandin glycerol esters and prostaglandin ethanolamides modulate intestinal epithelial hallmarks of colitis

Bestard-Escalas, Joan;Sasportes, Olivia;Ameraoui, Hafsa;González-Nicolau, Mar;Muccioli, Giulio;et.al.
(2026) Biochimica et Biophysica Acta. Molecular and Cell Biology of Lipids — Vol. 1871, n° 2, p. 159719 (2026)

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Abstract
Inflammatory bowel diseases (IBD) are chronic inflammatory disorders of the gastrointestinal tract with a high impact on patients' quality of life. The endocannabinoids 2-arachidonoylglycerol (2-AG) and N-arachidonoylethanolamine (AEA) are important modulators of inflammation. Their metabolism by cyclooxygenase (COX)-2 produces prostaglandin glycerol esters (PG-Gs) and prostaglandin ethanolamides (PG-EAs) that are endogenous analogues of the arachidonic acid- derived prostaglandins. Several PG-G and PG-EA possess interesting biological properties, notably in the context of colitis as we reported for PGD 2-G. However, while the properties of prostaglandins (such as PGE ) on epithelial cells in the context of colon inflammation are well described, the biological effects of PG-Gs and PG-EAs are unknown. 2 Here we used Caco-2 spheroids and mouse colon organoids to evaluate how PG-Gs and PG-EAs modulate three epithelial hallmarks of colitis, namely the epithelial barrier integrity, the production of cytokines, and the wound healing process. Importantly, we tested the corresponding prostaglandins in parallel. 2 When analyzing the effects of these prostanoids on the production of pro-inflammatory cytokines, we found that PGD-G did decrease the production of TNF PGE 2-G modulated the levels of TNF α , MIP2 α α and MCP-1 in activated Caco-2 spheroids. On colon organoids, , and KC and improved the survival of colon organoids in a DSS- plating efficiency assay without affecting stem cell dynamics. Our results put forth differential effects for PG- Gs, PG-EAs and the corresponding prostaglandins, and suggest that PGE 2-G could be an interesting lipid mediator in the context of colon epithelium inflammation.
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Bestard-Escalas, J., Sasportes, O., Ameraoui, H., González-Nicolau, M., Al Houayek, M., & Muccioli, G. (2026). The endocannabinoid-derived prostaglandin glycerol esters and prostaglandin ethanolamides modulate intestinal epithelial hallmarks of colitis. Biochimica et Biophysica Acta. Molecular and Cell Biology of Lipids, 1871(2), 159719. https://doi.org/10.1016/j.bbalip.2026.159719 (Original work published 2026)