IL-6 Produced by Kupffer Cells Induces STAT Protein Activation in Hepatocytes Early During the Course of Systemic Listerial Infections

• Published in: The Journal of immunology (1950) 1998-06, Vol.160 (12), p.6056-6061
• Main Authors: Gregory, Stephen H, Wing, Edward J, Danowski, Kristine L, van Rooijen, Nico, Dyer, Kevin F, Tweardy, David J
• Format: Article
• Language: English
• Subjects: Acute-Phase Proteins - metabolism; Animals; DNA-Binding Proteins - metabolism; Female; Interleukin-6 - biosynthesis; Interleukin-6 - genetics; Kupffer Cells - metabolism; Kupffer Cells - microbiology; Listeriosis - immunology; Liver - metabolism; Liver - microbiology; Mice; Mice, Inbred C57BL; STAT1 Transcription Factor; STAT3 Transcription Factor; Trans-Activators - metabolism
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.160.12.6056

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.