Kupffer cell depletion by CI₂MDP‐liposomes alters hepatic cytokine expression and delays liver regeneration after partial hepatectomy

Abstract

We conclude that KCs are important for hepatocyte regeneration after PH. Delayed liver regeneration in KC-depleted rats can be explained, at least in part, by an imbalanced hepatic cytokine expression, thereby suppressing important growth-stimulating cytokines.

Advances in gene therapy of liver cirrhosis: a review

“…Overexpression of TNF-α promoted liver regeneration potently after partial hepatectomy. Meijer et al strengthened the common point of view that Kupffer cell depletion, physically induced with dichloromethylene-diphosphonate, resulted in an imbalanced hepatic cytokine expression, thereby suppressing important growth-stimulating factors, including HGF and TNF-α [82] . Similar results were found in alcoholic cirrhosis [83] .…”

Platelet and Liver Regeneration

“…Kupffer cells have been postulated to play a key role in liver regeneration after partial hepatectomy, and they could produce important biologically-active mediators that have both stimulatory and inhibitory influence on hepatocyte proliferation after hepatectomy (Boulton et al, 1998). Except for a report stating augmentation of the early phase of liver regeneration with Kupffer cell depletion (Meijer et al, 2000), depletion of Kupffer cells is basically well-known www.intechopen.com . Effects of inhibitor of S1P and S1P on excretion of IL-6 from LSECs (A) Excretion of IL-6 from LSECs was evaluated using a specific antagonist for S1P2 receptors.…”

Cellular and Molecular Cascades during Liver Regeneration

“…41 When macrophages are ablated using liposomal clodronate followed by a PHx there is a delayed proliferative response from hepatocytes and the size of the remnant liver at 96 hours post-surgery is significantly less in Kupffer cell depleted rats. 41 This suggests that cytokines and growth factors secreted by macrophages are important for proliferative responses. Expression of key cytokines involved in liver regeneration are also down regulated at the mRNA level, this includes, IL-6, IL-10, TNF, HGF, and TGF-β1 at 4 hours post-PHx.…”

“…When Hh signaling is blocked after a PHx, via cyclopamine, there is reduced expression of numerous progenitor markers such as α-fetoprotein (AFP), Factor-inducible 14 Sinusoidal endothelial cell Spatiotemporal regulation in proliferation kinetics of hepatocytes and endothelial cells [28][29][30] Kupffer cell Secrete wnt ligands that control hepatocyte proliferation in a timely manner, wnt3a secretion promotes differentiation of hepatic progenitor cells into hepatocytes. 41,45 Stellate cell…”