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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
Author(s) -
KowalskiSaunders Peter W. J.,
Winwood Paul J.,
Arthur Michael J. P.,
Wright Ralph
Publication year - 1992
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.1840160320
Subject(s) - albumin , acute phase protein , tumor necrosis factor alpha , cytokine , medicine , kupffer cell , interleukin , endocrinology , serum albumin , interleukin 6 , biology , immunology , inflammation
Decreased albumin synthesis by hepatocytes in liver injury is thought to occur in response to Kupffer cell–derived 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 factor–a) 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 (α 1 ‐antitrypsin and α 2 ‐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–α also inhibited albumin synthesis (p < 0.05, Wilcoxon's rank sum test, n = 5), interleukin‐6 having the greatest effect. After exposure to interleukin‐1 (30 U · ml −1 ) and tumor necrosis factor–α (300 U · ml −1 ), decreased albumin synthesis was followed by a rebound increase (n = 3). Our results 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 . (H EPATOLOGY 1992;16:733–741.)