engleski

Inhibition of macrophage polarization by caffeic acid: interplay between ROS, antioxidans, and inflammatory cytokines

Macrophages are important both to innate and adaptive immune responses and are known to differentiate into M1 or M2 phenotypes following activation. While M1 macrophages are highly pro‐inflammatory, microbicidal and anticancer ; M2 macrophages and the related tumor associated macrophages (TAMs) regulate tissue remodeling and angiogenesis and can display immunomodulatory activity. It is demonstrated that production of reactive oxygen species (ROS), critical for the activation and functions of M1 macrophages, is also necessary for the differentiation of M2 macrophages and TAMs, and that antioxidant therapy blocks TAMs differentiation and tumorigenesis in mouse models of cancer. In order to study how caffeic acid, a natural antioxidant, affects macrophage function, polarization and tumor growth, we injected mice with Ehrlich ascites tumor (EAT) cells and treated them for 10 days with caffeic acid in a dose of 40 and/or 80 mg kg‐1. Macrophage polarization was further characterized by quantifying secreted pro‐ and anti‐inflammatory cytokines. Caffeic acid may increase the cytotoxic actions of macrophages and inhibit tumor growth ; inhibitory activity on TAMs may be mediated through its antioxidative activity. Taken together, we conclude that the continuous administration of the ROS inhibitor caffeic acid efficiently blocked the occurrence of TAMs and markedly suppressed tumorigenesis in mouse cancer models. Targeting TAMs by blocking ROS can be a potentially effective method for cancer treatment.

tumor ; macrophage polarization ; caffeic acid ; oxidative stress ; immunomodulation

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