Interferon-γ and tumor necrosis factor-α exert their antirickettsial effect via induction of synthesis of nitric oxide

Hui Min Feng, David H. Walker

Research output: Contribution to journalArticlepeer-review

51 Scopus citations

Abstract

How the host defenses control rickettsiae in the cytosol of nonphagocytic host cells, where they are not exposed to antibodies or phagocytes, has posed a difficult question. Rickettsia conorii infection of a mouse fibroblast cell line was inhibited in a dose-dependent manner by nitrogen oxide synthesized by eukaryotic host cells stimulated by interferon-γ or tumor necrosis factor-α. L-arginine was the source of the nitric oxide as demonstrated by competitive inhibition by N(G)-monomethyl-L-arginine. Nitric oxide synthesis required host cell protein synthesis and had an approximately 48-hour lag phase following cytokine stimulation. At low doses of interferon-γ and tumor necrosis factor-α, which had no detectable response as single agents, dramatic synergistic nitric oxide synthesis and antirickettsial effects were observed.

Original languageEnglish (US)
Pages (from-to)1016-1023
Number of pages8
JournalAmerican Journal of Pathology
Volume143
Issue number4
StatePublished - 1993

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Fingerprint Dive into the research topics of 'Interferon-γ and tumor necrosis factor-α exert their antirickettsial effect via induction of synthesis of nitric oxide'. Together they form a unique fingerprint.

Cite this