Reversible inhibition of albumin production by rat hepatocytes maintained on a laminin-rich gel (Engelbreth-Holm-Swarm) in response to secretory products of Kupffer cells and cytokines
✍ Scribed by Dr. Peter W. J. Kowalski-Saunders; Paul J. Winwood; Michael J. P. Arthur; Ralph Wright
- Publisher
- John Wiley and Sons
- Year
- 1992
- Tongue
- English
- Weight
- 913 KB
- Volume
- 16
- Category
- Article
- ISSN
- 0270-9139
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✦ Synopsis
Decreased albumin synthesis by hepatocytes in liver
injury is thought to occur in response to Kupffer cellderived acute-phase cytokines. In this study we used hepatocytes maintained in a differentiated phenotype, by culture on a laminin-rich gel substratum (Engelbreth-Holm-Swarm matrix), to investigate the effects of Kupffer cell-conditioned medium and purified cytokines (interleukin-1, interleukin-6 and tumor necrosis f a c t o r 4 on albumin synthesis. Kupffer cell-conditioned medium caused a reversible decrease in albumin synthesis to 64.7% of control (p < 0.01, Wilcoxon's rank sum test, n = 11) on day 2. Repeated doses caused further dose-dependent reversible responses. The same result was obtained when protease inhibitors (a,-antitrypsin and %-macroglobulin) were added to Kupffer cell-conditioned medium (n = 3), thus eliminating the potential effect of matrix degradation. Pure interleukin-1, interleukin-6 and tumor necrosis factor-also inhibited albumin syn- thesis (p < 0.05, Wilcoxon's rank sum test, n = 5), interleukin-6 having the greatest effect. After exposure to interleukin-1 (30 U -m l -' ) and tumor necrosis factor-a (300 U .ml-*), decreased albumin synthesis was followed by a rebound increase (n = 3). Our d t s support the hypothesis that reduced albumin synthesis in the acute-phase response is modulated by cytokines released from Kupffer cells. Moreover, our results suggest that hepatocytes may exhibit a compensatory increase in albumin synthesis after cytokine withdrawal. These findings may be of physiological importance in the recovery from injury and the acutephase response in vivo. (HEPATOLOGY 1992;16733-741.) In liver injury a marked reduction occurs in albumin synthesis associated with the release of acute-phase proteins. Activated hepatic macrophages (Kupffer cells)