Effect of dominant negative transforming growth factor-β receptor type II on cytotoxic activity of RAW 264.7, a murine macrophage cell line

Taek Lee Geun, Hyuk Hong Jun, Cheol Kwak, Jaesung Woo, Victoria Liu, Chung Lee, Isaac Yi Kim*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)6717-6724
Number of pages8
JournalCancer Research
Volume67
Issue number14
DOIs
StatePublished - Jul 15 2007

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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