The study investigates the anti-inflammatory properties of epoxyeicosatrienoic acids (EETs), which are products of cytochrome P450 epoxygenases. The researchers identified CYP2J2 as a key enzyme responsible for EET production in human endothelial cells. EETs, particularly [11,12]-EET, were found to inhibit cytokine-induced endothelial cell adhesion molecule expression and prevent leukocyte adhesion to the vascular wall by inhibiting NF-κB and IκB kinase. These effects were independent of EETs' membrane-hyperpolarizing properties, suggesting a nonvasodilatory role in vascular inflammation. The study also demonstrated that EETs repress VCAM-1 gene transcription through the inhibition of kB cis-acting elements and prevent NF-κB subunit Rel A nuclear translocation. In an in vivo model, [11,12]-EET reduced TNF-α-induced mononuclear cell adhesion and increased mononuclear cell rolling, indicating its therapeutic potential for vascular and nonvascular inflammatory disorders.The study investigates the anti-inflammatory properties of epoxyeicosatrienoic acids (EETs), which are products of cytochrome P450 epoxygenases. The researchers identified CYP2J2 as a key enzyme responsible for EET production in human endothelial cells. EETs, particularly [11,12]-EET, were found to inhibit cytokine-induced endothelial cell adhesion molecule expression and prevent leukocyte adhesion to the vascular wall by inhibiting NF-κB and IκB kinase. These effects were independent of EETs' membrane-hyperpolarizing properties, suggesting a nonvasodilatory role in vascular inflammation. The study also demonstrated that EETs repress VCAM-1 gene transcription through the inhibition of kB cis-acting elements and prevent NF-κB subunit Rel A nuclear translocation. In an in vivo model, [11,12]-EET reduced TNF-α-induced mononuclear cell adhesion and increased mononuclear cell rolling, indicating its therapeutic potential for vascular and nonvascular inflammatory disorders.