Okadaic acid triggers NFκB and STAT3 phosphorylation followed by a release of inflammatory markers in human and mouse endothelial cells
Year: 2026
Type: article
Abstract: 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 (IC 50 ) 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.
Source: Archives of Toxicology
Language: English
Topic: NF-κB Signaling Pathways
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $5,690
Awards: G1175115578, G121809054, G1855990336, G210041235, G2262748287, G2309174360, G2601397997, G2660406951, G279363373, G2920696644, G300979063, G3104197067, G34346518, G3480869486, G3518538256, G3681454997, G4042783231, G4092263876, G425668148, G430777504, G4442677895, G4526231891, G464105488, G5080475149, G5195188938, G5421974903, G5691684808, G67688110, G7084143925, G897484643, G99296377
OpenAlex ID: W7129066815