Chloroquine inhibits macrophage tumour necrosis factor-alpha mRNA transcription.
Although chloroquine administration in vivo following haemorrhage in mice decreases tumour necrosis factor-alpha (TNF-alpha) release by macrophage (M phi), the mechanism remains unknown. To study this, peritoneal M phi (pM phi) from unmanipulated, sham-operated and post-haemorrhage mice were isolated, treated with 0.13 mg/ml chloroquine for 2 hr, and then stimulated with lipopolysaccharide (LPS) for 48 hr. Pretreatment of pM phi from various groups of mice with chloroquine resulted in 75-90% inhibition of TNF-alpha release, determined by bioassay. Total RNA was isolated from pM phi and murine M phi-derived cell lines (P388D1 and RAW 264.7), stimulated with LPS for 0.5 or 1 hr, respectively, and Northern blot analysis for TNF-alpha mRNA performed. Chloroquine inhibited TNF-alpha mRNA expression without interfering with mRNA stability, suggesting that this agent reduces M phi TNF-alpha release by disrupting TNF-alpha gene transcription.
Zhu
X
X
Department of Surgery, Michigan State University, East Lansing 48824-1315.
Ertel
W
W
Ayala
A
A
Morrison
M H
MH
Perrin
M M
MM
Chaudry
I H
IH
D000818:Animals; D002738:Chloroquine / Q000494:pharmacology*; D006470:Hemorrhage / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D010529:Peritoneal Cavity / Q000166:cytology; D012333:RNA, Messenger / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000276:immunology
D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D002738:Chloroquine