Hepatocytes enhance effects of lipopolysaccharide on liver nonparenchymal cells through close cell interactions

Melanie J. Scott*, Shubing Liu, Grace L. Su, Yoram Vodovotz, Timothy R. Billiar

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

31 Scopus citations


The response to lipopolysaccharide (LPS) in the liver is complex, requiring cell-to-cell interactions between hepatocytes and liver nonparenchymal cells (NPC), in particular, Kupffer cells. Previous studies show that cytokines produced by Kupffer cells stimulated with LPS can, in turn, activate hepatocytes. In the present study, we sought to examine whether the reverse, hepatocyte (HC)-NPC interactions, is important in cytokine production in mixed cell cocultures. LPS-stimulated production of tumor necrosis factor (TNF)-α and interleukin (IL)-6 from NPC was augmented in mixed HC-NPC cocultures, as compared with NPC monocultures. This HC-NPC interaction was not observed when hepatocytes were cocultured with NPC from TLR4-mutant (C3H/HeJ) mice or CD14-deficient mice. The effect was partially lost when hepatocytes from lipopolysaccharide-binding protein (LBP)-deficient mice were cocultured with wild-type mice. These data indicate that functional TLR4 and CD14 are required for NPC production of cytokines and that at least one of the critical components from hepatocytes is LBP. The augmented cytokine production by mixed HC-NPC cocultures was abrogated when the cells were separated by a filter system, indicating that close cell interactions are also required for this interaction. Thus, interaction between hepatocytes and NPC are critical for cytokine secretion by NPC.

Original languageEnglish
Pages (from-to)453-458
Number of pages6
Issue number5
StatePublished - May 2005
Externally publishedYes


  • CD14
  • Cytokines
  • LBP
  • TLR4


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