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Improved Kupffer cell‐mediated cytokine production by micropatterned co‐culture with hepatocyte
Author(s) -
Lee Sang Ho,
Zinchenko Yekaterina S.,
Coger Robin N.,
Clemens Mark G.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a414
Subject(s) - hepatocyte , bioartificial liver device , microbiology and biotechnology , lipopolysaccharide , messenger rna , albumin , cell culture , chemistry , stimulation , biology , immunology , endocrinology , in vitro , biochemistry , genetics , gene
There is growing evidence that co‐culture of hepatocytes with hepatic non‐parenchymal cells provides improved hepatocyte function in a bioartificial liver (BAL) device. Moreover, controlled spatial relationships using a micropatterned culture surface further improves hepatocyte function; however, the function of non‐parenchymal cells is not well understood. Therefore, we examined the effect of a micropatterned surface on the function of Kupffer cells (KCs) co‐cultured with hepatocytes. Toward this goal, we compared biological functions of hepatocytes and mRNA expressions of KC‐derived cytokines with or without endotoxin stimulation. The amounts of albumin and urea from hepatocytes on the micropatterned surface were remarkably increased as compared with random co‐culture. The KCs, which were confirmed by CD11b mRNA, showed similar alterations of TNF‐alpha and IL‐1beta mRNA levels through the lipopolysaccharide (LPS) treatment in both co‐culture conditions. However, expression of IL‐6 mRNA in the micropatterned group was increased two fold over random co‐culture before and after endotoxin spiking. In contrast, the level of IL‐10 mRNA revealed no significant increases in response to LPS as compared with extensive induction in random co‐culture. These results suggest that micropatterned configurations provide better environment for the functional response of KCs. The presence of IL‐6 may be responsible for this phenomenon. Supported by NIH (R01 DK58503) and the Whitaker Foundation (RG‐01‐0343)