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 x 10(1) to 4.0 x 10(7) CFU/mL culture medium), as well as highly purified PepG and LTA (0-100 microg/mL). Lipopolysaccharide (LPS) at 1 microg/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-alpha) and interleukin-6 (IL-6) in plasma or culture supernatants were assessed by enzyme immuno assays. TNF-alpha 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-alpha 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-alpha 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 microg/mL) than of PepG (100 microg/mL) was sufficient to induce a substantial production of both TNF-alpha and IL-6 in the Kupffer cells. TNF-alpha 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.
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 x 10(1) to 4.0 x 10(7) CFU/mL culture medium), as well as highly purified PepG and LTA (0-100 microg/mL). Lipopolysaccharide (LPS) at 1 microg/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-alpha) and interleukin-6 (IL-6) in plasma or culture supernatants were assessed by enzyme immuno assays. TNF-alpha 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-alpha 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-alpha 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 microg/mL) than of PepG (100 microg/mL) was sufficient to induce a substantial production of both TNF-alpha and IL-6 in the Kupffer cells. TNF-alpha 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.
Authors: Yinzhong Zhang; Xinchun Lin; Kiyokazu Koga; Koichiro Takahashi; Helena M Linge; Adriana Mello; Teresina Laragione; Percio S Gulko; Edmund J Miller Journal: Mol Med Date: 2011-04-28 Impact factor: 6.354
Authors: Maria K Dahle; Gunhild Øverland; Anders E Myhre; Jon Fredrik Stuestøl; Thomas Hartung; Claus Danckert Krohn; Øystein Mathiesen; Jacob E Wang; Ansgar O Aasen Journal: Infect Immun Date: 2004-10 Impact factor: 3.441
Authors: Peter M Grin; Dhruva J Dwivedi; Kevin M Chathely; Bernardo L Trigatti; Annik Prat; Nabil G Seidah; Patricia C Liaw; Alison E Fox-Robichaud Journal: Sci Rep Date: 2018-07-12 Impact factor: 4.379