Lipoteichoic acid is a potent inducer of cytokine production in rat and human Kupffer cells in vitro

Gunhild Øverland, Sigfried Morath, Arne Yndestad, Thomas Hartung, Christoph Thiemermann, Simon J. Foster, Bård Smedsrød, Øystein Mathisen, Pål Aukrust, Ansgar O. Aasen, Jacob E. Wang

Research output: Contribution to journalArticle

Abstract

Background: Kupffer cells have been proposed to be a major cellular origin of pro-inflammatory mediators in sepsis. However, the cytokine response of Kupffer cells to gram-positive bacteria and their endotoxins peptidoglycan (PepG) and lipoteichoic acid (LTA) has never previously been studied. Materials and Methods: Primary cultures of rat and human Kupffer cells were exposed to live Staphylococcus aureus (S. aureus) (4.0 × 101 to 4.0 × 107 CFU/mL culture medium), as well as highly purified PepG and LTA (0-100 μg/mL). Lipopolysaccharide (LPS) at 1 μg/mL was used for control. In parallel experiments, whole blood obtained from the same rats was stimulated in a similar manner. Accumulation of the proinflammatory cytokines tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in plasma or culture supernatants were assessed by enzyme immuno assays. TNF-α and IL-6 mRNA were analyzed by real-time RT-PCR. Results: PepG and LTA, as well as live S. aureus, induced the production of TNF-α and IL-6 in Kupffer cells from both species in a time- and dose-dependent manner. Whereas PepG was a more potent inducer of TNF-α and IL-6 in whole blood, the opposite seemed to be the case in Kupffer cells. In fact, a 100-fold lower concentration of LTA (1 μg/mL) than of PepG (100 μg/mL) was sufficient to induce a substantial production of both TNF-α and IL-6 in the Kupffer cells. TNF-α and IL-6 mRNA were induced correspondingly. Conclusion: Our results support the contention that gram-positive bacteria may activate cytokine production in Kupffer cells during bacteremia and suggest that LTA is important in this interaction.

Original languageEnglish (US)
Pages (from-to)181-191
Number of pages11
JournalSurgical infections
Volume4
Issue number2
DOIs
StatePublished - Jan 1 2003
Externally publishedYes

ASJC Scopus subject areas

  • Surgery
  • Microbiology (medical)
  • Infectious Diseases

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    Øverland, G., Morath, S., Yndestad, A., Hartung, T., Thiemermann, C., Foster, S. J., Smedsrød, B., Mathisen, Ø., Aukrust, P., Aasen, A. O., & Wang, J. E. (2003). Lipoteichoic acid is a potent inducer of cytokine production in rat and human Kupffer cells in vitro. Surgical infections, 4(2), 181-191. https://doi.org/10.1089/109629603766956979