Effects of OX40–OX40L Interaction on the Nuclear Factor of Activated T Cells c1 in ApoE-Deficient Mice

We previously reported the emerging role of OX40–OX40L interaction in inflammation and atherosclerosis. However, the mechanism by which OX40–OX40L interaction contributes to pathogenesis is poorly understood. This study investigated the effects of OX40–OX40L interaction on the nuclear factor of activated T cells c1 (NFATc1) in ApoE^−/− mice. Atherosclerotic plaque was induced via rapid perivascular carotid collar placement in ApoE^−/− mice. The expression levels of OX40, OX40L, and NFATc1 in the lymphocytes were measured via real-time polymerase chain reaction and flow cytometry. The presence of NFATc1 in the atherosclerotic plaque was detected via immunohistochemistry, and the level of IL-4 was measured via enzyme-linked immunosorbent assay. The expression level of NFATc1 significantly increased in atherosclerotic lesion and in the leukocytes from the ApoE^−/− mice. After stimulating OX40–OX40L interaction, the mRNA and protein expression levels of NFATc1 in the lymphocytes significantly increased. Meanwhile, anti-OX40LmAb significantly suppressed the expression of NFATc1 in the leukocytes and substantially elevated the level of IL-4. NFATc1 inhibitor markedly suppressed IL-4 production. This study suggests that OX40–OX40L interaction regulates the expression of NFATc1, which may play a critical role in atherosclerotic plaque formation, and may therefore have implications with pathophysiology of atherosclerosis.