RT Journal Article
T1 Okadaic acid triggers NFκB and STAT3 phosphorylation followed by a release of inflammatory markers in human and mouse endothelial cells
A1 Nyback, Klara
A1 Alfonso Rancaño, María Amparo
A1 Alvariño Romero, Rebeca
A1 Suzuki, Toshiyuki
A1 Watanabe, Ryuichi
A1 Uchida, Hajime
A1 Rodríguez Vieytes, Mercedes
A1 Botana López, Luis Miguel
K1 Okadaic acid
K1 Inflammation
K1 Endothelial cells
K1 NFkB
K1 STAT3
AB Okadaic 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.
PB Springer
YR 2026
FD 2026-02-17
LK https://hdl.handle.net/10347/46676
UL https://hdl.handle.net/10347/46676
LA eng
NO Nyback, 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/s00204-026-04320-3
NO Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature.
NO The research leading to these results has received funding from the following grants. From Conselleria de Cultura, Educacion e Ordenación Universitaria, Xunta de Galicia, GRC (GI-1682-2025). From Ministerio de Ciencia e Innovación, Grant CPP2021-008447 funded by MCIN/AEI/10.13039/501100011033, and by The European Union NextGeneration EU/PRT. From Ministerio de Ciencia, Innovación y Universidades, PID2023-149618OBI00. From European Union Interreg EAPA-0032/2022 – BEAPMAR, and EAPA_0130/2024 – REVALGAE (cofunded by the EU), from European Union HORIZON-CL6-2023-CIRCBIO-01 COMBO−101135438 and BioToxDoc 101119901.
DS Minerva
RD 23 abr 2026