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remains to be established whether KC generated products directly affect the number
(apoB) and composition of secreted VLDL. Using rat primary cells, we show here that
hepatocytes respond to stimulation by soluble mediators released by LPS-stimulated
Kupffer cells with enhanced secretion of apoB and triglycerides in phospholipid-rich
VLDL particles. Unstimulated KC products also augmented the secretion of normal VLDL,
doubling apoB mRNA abundance. IL-1β treatment resulted in concentration-dependent
increases of hepatocyte apoB mRNA and protein secretion, increases that were greater,
but not additive, when combined with IL-6 and TNF-α. Lipid secretion and MTP mRNA
levels were unaffected by cytokines. In summary: (i) enhanced secretion of
phospholipid-rich VLDL particles is a net hepatocyte response to LPS-stimulated KC
products, which gives a clue about the local role of Kupffer cells in septic
dyslipidemia induction; and (ii) pro-inflammatory cytokines act redundantly to
enhance apoB secretion involving translational apoB up-regulation, but other humoral
components or KC mediators are necessary to accomplish increased lipid
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