Open AccessDelayed growth of EL4 lymphoma in SR‐A‐deficient mice is due to upregulation of nitric oxide and interferon‐γ production by tumor‐associated macrophages
Author(s) -
Komohara Yoshihiro,
Takemura Kenichi,
Lei Xiao Feng,
Sakashita Naomi,
Harada Mamoru,
Suzuki Hiroshi,
Kodama Tatsuhiko,
Takeya Motohiro
Publication year - 2009
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2009.01296.x
Subject(s) - downregulation and upregulation , nitric oxide , macrophage , interferon gamma , scavenger receptor , nitric oxide synthase , in vitro , biology , interferon , receptor , chemistry , cytokine , cancer research , immunology , microbiology and biotechnology , endocrinology , biochemistry , lipoprotein , cholesterol , gene
Class A scavenger receptors (SR‐A, CD204) are highly expressed in tumor‐associated macrophages (TAM). To investigate the function of SR‐A in TAM, wild‐type and SR‐A‐deficient (SR‐A −/− ) mice were injected with EL4 cells. Although these groups of mice did not differ in the numbers of infiltrating macrophages and lymphocytes and in neovascularization, SR‐A −/− mice had delayed growth of EL4 tumors. Expression of inducible nitric oxide (NO) synthase and interferon (IFN)‐γ mRNA increased significantly in tumor tissues from SR‐A −/− mice. Engulfment of necrotic EL4 cells induced upregulation of NO and IFN‐γ production by cultured macrophages, and production of NO and IFN‐γ increased in SR‐A −/− macrophages in vitro . IFN‐β production by cultured macrophages was also elevated in SR‐A −/− macrophages in vitro . These results suggested that the antitumor activity of macrophages increased in SR‐A −/− mice because of upregulation of NO and IFN‐γ production. These data indicate an important role of SR‐A in regulating TAM function by inhibiting toll‐like receptor (TLR)4–IFN‐β signaling. ( Cancer Sci 2009); 00: 000–000)