title: Macrophage-adipocyte interaction: marked interleukin-6 production by lipopolysaccharide.
abstract: OBJECTIVE
  Recent studies suggested macrophages were integrated in adipose tissues, interacting with adipocytes, thereby exacerbating inflammatory responses. Persistent low-grade infection by gram-negative bacteria appears to promote atherogenesis. We hypothesized a ligand for toll-like receptor 4 (TLR4), bacterial lipopolysaccharide (LPS), would further exaggerate macrophage-adipocyte interaction.
  
  
  METHODS
  RAW264.7 macrophage cell line and differentiated 3T3-L1 preadipocytes were co-cultured using transwell system. As a control, each cell was cultured independently. After incubation of the cells with or without Escherichia coli LPS, tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 production was evaluated.
  
  
  RESULTS
  Co-culture of macrophages and adipocytes with low concentration of Escherichia coli LPS (1 ng/mL) markedly up-regulated IL-6 production (nearly 100-fold higher than that of adipocyte culture alone, p < 0.01), whereas TNF-alpha production was not significantly influenced. This increase was partially inhibited by anti-TNF-alpha neutralizing antibody. Recombinant TNF-alpha and LPS synergistically up-regulated IL-6 production in adipocytes. However, this increase did not reach the level of production observed in co-cultures stimulated with LPS.
  
  
  CONCLUSIONS
  A ligand for TLR-4 stimulates macrophages to produce TNF-alpha. TNF-alpha, thus produced, cooperatively up-regulates IL-6 production with other soluble factors secreted either from adipocytes or macrophages in these cells. Markedly up-regulated IL-6 would greatly influence the pathophysiology of diabetes and its vascular complications.
authors: Department of Pathophysiology-Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors: Akiko
authors: A
authors: Yamashita
authors: Yoshihiko
authors: Y
authors: Soga
authors: Yoshihiro
authors: Y
authors: Iwamoto
authors: Sayuri
authors: S
authors: Yoshizawa
authors: Hirotaka
authors: H
authors: Iwata
authors: Susumu
authors: S
authors: Kokeguchi
authors: Shogo
authors: S
authors: Takashiba
authors: Fusanori
authors: F
authors: Nishimura
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D002450:Cell Communication / Q000502:physiology*; D002460:Cell Line; D002478:Cells, Cultured; D018920:Coculture Techniques; D004357:Drug Synergism; D015850:Interleukin-6 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D051197:Toll-Like Receptor 4 / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology
chemical_list: D015850:Interleukin-6; D008070:Lipopolysaccharides; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha