Transforming growth factor-β (TGF-β) is a potent suppressor of the immune system. In the present study, we investigated the effect of TGF-β resistance on a murine macrophage cell line, RAW 264.7, by overexpressing a dominant negative TGF-β receptor type II (TβRIIDN) construct. As expected, TβRIIDN-expressing RAW cells, designated as RAW-TβRIIDN, were resistant to TGF-β signaling. When these cells were cocultured with the murine renal cell carcinoma cell line, Renca, a dramatic increase in apoptosis of Renca cells was observed. Simultaneously, elevated levels of inducible nitric oxide synthase (iNOS) and tumor necrosis factor-α (TNF-α) in association with IFN-γ were detected in RAW-TβRIIDN cells. When the effects of TNF-α and iNOS were neutralized through the use of neutralizing antibody and NG-methyl-L- arginine, respectively, the enhanced cytotoxicity of TβRIIDN-RAW cells was partially reversed. Taken together, these results show that TGF-β-resistant RAW 264.7 murine macrophage cells have increased cytotoxic activity that is in part mediated by iNOS and TNF-α.
ASJC Scopus subject areas
- Cancer Research