The role of S100A8 on nitric oxide production of macrophages

Abstract

Various studies have shown that nitric oxide (NO) from macrophages in tumor microenvironment can promote tumor progression in multiple ways including inflammation, transformation, altered metabolism, tumor angiogenesis and metastasis. Even though S100A8 of macrophages is well known for involving in promoting the inflammatory response in infection, its correlation with nitric oxide production in tumor microenvironment is not fully understood. Therefore, we hypothesized that S100A8 activated nitric oxide production of macrophages thereby promoting tumor development. To test our hypothesis, we measured NO level and performed western blot analysis against S100A8. Not only co-culture of LLC or treatment of LLC sup but also S100A8 significantly induced NO production through NFkB/iNOS signaling pathway in bone marrow derived macrophages (BMDM). We also observed an increased expression of S100A8 in BMDMs co-cultured with Lewis Lung Carcinoma (LLC) or treated with LLC supernatant. Furthermore, we found out that BMDM co-cultured with LLC increased TNFα expression and it promoted S100A8 expression in autocrine manner. In conclusion, macrophages that are infiltrated into tumor microenvironment increased TNFα-induced S100A8 expression and it promoted NO production through S100A8-dependent NFkB/iNOS axis.