Nyback, KlaraAlfonso Rancaño, María AmparoAlvariño Romero, RebecaSuzuki, ToshiyukiWatanabe, RyuichiUchida, HajimeRodríguez Vieytes, MercedesBotana López, Luis Miguel2026-04-132026-04-132026-02-17Nyback, K., Alfonso, A., Alvariño, R., Suzuki, T., Watanabe, R., Uchida, H., Rodríguez Vieytes, M., & Botana, L.M. (2026) Okadaic acid triggers NFκB and STAT3 phosphorylation followed by a release of inflammatory markers in human and mouse endothelial cells. Archives of Toxicology, 1-11. https://doi.org/10.1007/s00204-026-04320-3https://hdl.handle.net/10347/46676Okadaic acid (OA) is a lipophilic phycotoxin that causes acute diarrhoea when ingested. OA is an inhibitor of protein phosphatase 2 A, but the mechanism of toxicity behind the diarrhoea remains unclear. OA modulated inflammatory markers in epithelial cells, however, the effect on endothelial cells, with a key role in the inflammatory cascade, has not been previously addressed. Therefore, the aim of the present work was to test the effect of OA in human (HMEC-1) and mouse (MS1) endothelial cells. After 3, 6 and 24 h of incubation in the presence of OA (10-1000 nM) cell viability was significantly reduced, showing a higher effect on human cells with half inhibitory concentrations (IC50) in HMEC-1 cells five times lower than in mouse cells. Furthermore, when cells were treated with OA, significant amounts of the proinflammatory mediators ROS, CD147, IL-6 and monocyte chemoattractant protein 1 (MCP-1) were detected. Some of these effects were observed only in HMEC-1 cells and around three hours earlier, pointing again to a higher sensitivity in human models. Finally, OA triggered phosphorylation of NFκB at 100 nM after 3 and 6 h of treatment, while the signal transducer and activator of transcription 3 (STAT3) was increased after 3 h but decreased after 6 h in both cell lines. Altogether, these data suggest that the toxic effect of OA in endothelial cells could be related with the activation of the inflammatory cascade.engThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.o rg/licenses/by/4.0/.Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/Okadaic acidInflammationEndothelial cellsNFkBSTAT3journal article10.1007/s00204-026-04320-31432-0738open access