Macrophage-adipocyte interaction: marked interleukin-6 production by lipopolysaccharide.
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.
Yamashita
Akiko
A
Department of Pathophysiology-Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Soga
Yoshihiko
Y
Iwamoto
Yoshihiro
Y
Yoshizawa
Sayuri
S
Iwata
Hirotaka
H
Kokeguchi
Susumu
S
Takashiba
Shogo
S
Nishimura
Fusanori
F
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
D015850:Interleukin-6; D008070:Lipopolysaccharides; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha