IL-6 produced by Kupffer cells induces STAT protein activation in hepatocytes early during the course of systemic listerial infections.
Kupffer cells were the principal source of IL-6 produced in the livers of mice following i.v. inoculation of Listeria monocytogenes. IL-6 mRNA expression and the production of IL-6 were reduced drastically within the nonparenchymal liver cell population derived from mice rendered Kupffer cell depleted by pretreatment with liposome-encapsulated dichloromethylene diphosphonate. A sharp increase in the appearance of activated STAT3 occurred in extracts of purified hepatocytes derived from normal mice infected i.v. with Listeria. Remarkably, the kinetics of this increase overlapped IL-6 mRNA expression by Kupffer cells; each peaked at approximately 30 min postinfection. No increase in STAT3 activation was observed in IL-6-deficient or Kupffer cell-depleted animals. The results of these experiments indicate that the synthesis of IL-6 and the activation of STAT3 within hepatocytes are critical functions of Kupffer cells occurring very early during the course of systemic listerial infections.
Gregory
S H
SH
Department of Medicine, University of Pittsburgh School of Medicine, PA 15213, USA. gregory@med1.dept-med.pitt.edu
Wing
E J
EJ
Danowski
K L
KL
van Rooijen
N
N
Dyer
K F
KF
Tweardy
D J
DJ
D000209:Acute-Phase Proteins / Q000378:metabolism*; D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D007728:Kupffer Cells / Q000378:metabolism* / Q000382:microbiology; D008088:Listeriosis / Q000276:immunology*; D008099:Liver / Q000378:metabolism* / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism*
D000209:Acute-Phase Proteins; D004268:DNA-Binding Proteins; D015850:Interleukin-6; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; C494080:Stat1 protein, mouse; C494087:Stat3 protein, mouse; D015534:Trans-Activators