Work

Inhibition of CTLA-4 accelerates atherosclerosis in hyperlipidemic mice by modulating the Th1/Th2 balance via the NF-κB signaling pathway

Year: 2024

Type: article

Abstract: Objective: Though an increased risk of atherosclerosis is associated with anti-CTLA-4 antibody therapy, the underlying mechanisms remain unclear. Methods: T cells secreting IFN-γ and IL-4, which represent Th1 and Th2 cells respectively, were detected by flow cytometry and real-time PCR. Protein levels of p-IκBα, IκBα, p-p65, and p65 were determined by Western blot. Results: T cell differentiation toward the Th1 type, as indicated by an increase in the Th1/Th2 ratio. Compared to the anti-IgG group, treatment with anti-CTLA-4 antibody significantly elevated the protein levels of p-IκBα and p-p65, as well as the mRNA levels of TNF-α, IL-6, ICAM-1, and VCAM-1. Inhibiting the NF-κB signaling pathway attenuated the overall pathological phenotype induced by the anti-CTLA-4 antibody treatment. Conclusion: Anti-CTLA-4 treatment promotes the progression of atherosclerosis by activating NF-κB signaling and modulating the Th1/Th2 balance. Our results provide a rationale for preventing and/or treating atherosclerosis accelerated by anti-CTLA-4 antibody therapy in cancer patients.

Source: Heliyon

DOI: 10.1016/j.heliyon.2024.e37278