Hepatic Regeneration Induces Transient Acute Phase Reaction: Systemic Elevation of Acute Phase Reactants and Soluble Cytokine Receptors

Abstract

The growth factors present during liver regeneration partially overlap with the regulators of the hepatic acute phase response. We analysed the acute phase reaction and changes in soluble cytokine receptors after partial hepatectomy, when tissue injury inducing acute phase reaction and major reduction of liver mass occur simultaneously. Three acute phase proteins and mRNAs were determined by ELISA and northern blot hybridisation in rats. Serum levels of IL-6 and three soluble cytokine receptors (sTNF-alpha R I and II, sIL-6R) were detected by ELIBA or dot-blot assay. Time-course profiles of fibrinogen, alpha(2)-macroglobulin and haptoglobin proteins and mRNA are presented. Elevation of IL-6, soluble TNF-alpha receptors and soluble IL-6 receptor levels were also detected. The time-course of changes in haptoglobin concentration and elevation of soluble cytokine receptors is described by this in vivo experimental system. The results show good correlation with (post)transcriptional activation of immediate and delayed early gene products. These data suggest the involvement of both acute phase proteins and soluble cytokine receptors in the regulation of liver regeneration.

Clinical Significance of Joint Detection of Serum VEGF, SIL-2R and HGF in Patients with Primary Hepatocellular Carcinoma before and after Percutaneous Microwave Coagulation Therapy

“…The regenerative process of liver cells is influenced by multiple factors, including the factors respectively promoting and inhibiting the liver cell regeneration to maintain the starting and ending balance of liver regeneration (Fulop et al, 2001). HGF is the most important growth factor that promotes the liver regeneration in the process of liver regeneration.…”

Gene modulation associated with inhibition of liver regeneration in hepatitis B virus X transgenic mice

“…At the same time, Il-6, IL-1 and TNF-α, known to be hepatic mitogens, induce the acute-phase response (APR) [3,43] . During APR, the hepatic biosynthesis of SAA is up-regulated by proinflammatory cytokines, and the circulating concentration of SAA can increase up to 1000 fold.…”

“…The physiological transient induction of SAA appears to be indispensable for the precise regeneration rate after PH [3] . To investigate whether HBx expression was able to completely or partially inhibit SAA3 expression during PH, real time RT-PCR was performed on liver biopsies obtained at the time of PH (T0) and 48 h later from two LacZ or HBx-LacZ transgenic mice.…”

“…Regulation of SAA expression during the acute phase response depends on hepatic mitogens (Il-6, IL-1, TNF-α) [3] . As the expression of these cytokines is not significantly modified by HBx 48 h after PH, they are probably not implicated in the observed inhibition of SAA3 transcription in HBx-LacZ transgenic mice.…”

“…TNF-www.wjgnet.com α-induced hepatocyte proliferation has been shown to involve the small GTPases (Ras and RhoA) necessary for cell cycle progression by stimulating the degradation of Cdk inhibitors (p21 Cip and p27 Kip1 ) [2] . The initiation factors governing liver regeneration partially overlap with regulators of the hepatic acute phase response (APR), which results in dramatic changes in the expression of acute phase response proteins following PH [3] . Hepatocyte growth factor (HGF) and transforming growth factor alpha (TGFα) further stimulate cell cycle progression, DNA synthesis and cell proliferation.…”