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

Hui Min Feng, David Walker

Research output: Contribution to journalArticle

49 Citations (Scopus)

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

Fingerprint

Interferons
Nitric Oxide
Tumor Necrosis Factor-alpha
Arginine
Rickettsia Infections
Rickettsia conorii
Rickettsia
Eukaryotic Cells
Phagocytes
Cytosol
Fibroblasts
Cytokines
Cell Line
Antibodies
Proteins

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Interferon-γ and tumor necrosis factor-α exert their antirickettsial effect via induction of synthesis of nitric oxide. / Feng, Hui Min; Walker, David.

In: American Journal of Pathology, Vol. 143, No. 4, 1993, p. 1016-1023.

Research output: Contribution to journalArticle

@article{1800aa21421b453a8d9835ad8313f722,
title = "Interferon-γ and tumor necrosis factor-α exert their antirickettsial effect via induction of synthesis of nitric oxide",
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.",
author = "Feng, {Hui Min} and David Walker",
year = "1993",
language = "English (US)",
volume = "143",
pages = "1016--1023",
journal = "American Journal of Pathology",
issn = "0002-9440",
publisher = "Elsevier Inc.",
number = "4",

}

TY - JOUR

T1 - Interferon-γ and tumor necrosis factor-α exert their antirickettsial effect via induction of synthesis of nitric oxide

AU - Feng, Hui Min

AU - Walker, David

PY - 1993

Y1 - 1993

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0027816928&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027816928&partnerID=8YFLogxK

M3 - Article

C2 - 8213997

AN - SCOPUS:0027816928

VL - 143

SP - 1016

EP - 1023

JO - American Journal of Pathology

JF - American Journal of Pathology

SN - 0002-9440

IS - 4

ER -