scholarly journals Interleukin-6 Downregulates Factor XII Production by Human Hepatoma Cell Line (HepG2)

Blood ◽  
1997 ◽  
Vol 90 (4) ◽  
pp. 1501-1507
Author(s):  
Franca Citarella ◽  
Angelina Felici ◽  
Mieke Brouwer ◽  
John Wagstaff ◽  
Antonio Fantoni ◽  
...  
Keyword(s):  
Acute Phase ◽  
Acute Phase Response ◽  
Acute Phase Proteins ◽  
Acute Phase Protein ◽  
Hepatoma Cell ◽  
Hepatoma Cell Line ◽  
Factor Xii ◽  
Human Hepatoma Cell ◽  
Phase Protein ◽  
Hepatoma Cell Line Hepg2

Involvement of the contact system of coagulation in the pathogenesis of various inflammatory diseases is suggested by reduced plasma levels of factor XII (Hageman factor) and prekallikrein generally considered to result from activation of the contact system. However, in many of these diseases patients develop an acute-phase response and, therefore, an alternative explanation for the decreased levels of factor XII could be the downregulation of factor XII gene expression in the liver as described for negative acute-phase proteins. We report here that interleukin-6 (IL-6), the principal cytokine mediating the synthesis of most acute-phase proteins in the liver, downregulates the production of factor XII by the human hepatoma cell line HepG2 by up to 75%. The decrease in protein secretion correlated with an equivalent decrease of factor XII mRNA likely indicating a pretranslational control of factor XII gene expression by IL-6. Downregulation of factor XII production by IL-6 in vitro parallelled that of transthyretin, a known negative acute-phase protein. Moreover, we show that, in patients developing an acute-phase response after immunotherapy with IL-2, plasma levels of factor XII correlate (r = .76, P < .0001) with those of transthyretin. Taken together, these results suggest that factor XII behaves as a negative acute-phase protein.

scholarly journals Interleukin-6 Downregulates Factor XII Production by Human Hepatoma Cell Line (HepG2)

Blood ◽  
1997 ◽  
Vol 90 (4) ◽  
pp. 1501-1507 ◽  
Author(s):  
Franca Citarella ◽  
Angelina Felici ◽  
Mieke Brouwer ◽  
John Wagstaff ◽  
Antonio Fantoni ◽  
...  
Keyword(s):  
Acute Phase ◽  
Acute Phase Response ◽  
Acute Phase Proteins ◽  
Acute Phase Protein ◽  
Hepatoma Cell ◽  
Hepatoma Cell Line ◽  
Factor Xii ◽  
Human Hepatoma Cell ◽  
Phase Protein ◽  
Hepatoma Cell Line Hepg2

Abstract Involvement of the contact system of coagulation in the pathogenesis of various inflammatory diseases is suggested by reduced plasma levels of factor XII (Hageman factor) and prekallikrein generally considered to result from activation of the contact system. However, in many of these diseases patients develop an acute-phase response and, therefore, an alternative explanation for the decreased levels of factor XII could be the downregulation of factor XII gene expression in the liver as described for negative acute-phase proteins. We report here that interleukin-6 (IL-6), the principal cytokine mediating the synthesis of most acute-phase proteins in the liver, downregulates the production of factor XII by the human hepatoma cell line HepG2 by up to 75%. The decrease in protein secretion correlated with an equivalent decrease of factor XII mRNA likely indicating a pretranslational control of factor XII gene expression by IL-6. Downregulation of factor XII production by IL-6 in vitro parallelled that of transthyretin, a known negative acute-phase protein. Moreover, we show that, in patients developing an acute-phase response after immunotherapy with IL-2, plasma levels of factor XII correlate (r = .76, P < .0001) with those of transthyretin. Taken together, these results suggest that factor XII behaves as a negative acute-phase protein.

scholarly journals Monokines regulate glycosylation of acute-phase proteins.

1987 ◽  
Vol 166 (1) ◽  
pp. 253-258 ◽  
Author(s):  
A Mackiewicz ◽  
M K Ganapathi ◽  
D Schultz ◽  
I Kushner
Keyword(s):  
Cell Line ◽  
Acute Phase ◽  
Acute Phase Response ◽  
Acute Phase Proteins ◽  
Hepatoma Cell ◽  
Phase Response ◽  
Hepatoma Cell Line ◽  
Human Hepatoma Cell ◽  
Inflammatory Stimuli ◽  
Necrosis Factor

The acute-phase response to inflammatory stimuli, characterized by increased synthesis of acute-phase proteins (APP), is often accompanied by changes in the glycosylation patterns of some of these proteins. While expression of APP genes in hepatocytes is regulated by monokines, mechanisms governing changes in glycosylation are not known. Exposure of human hepatoma cell line Hep 3B to conditioned medium from LPS-activated human monocytes and to medium from the keratocarcinoma cell line COLO-16 led to increased synthesis of alpha 1 proteinase-inhibitor and ceruloplasmin and to alterations of their glycosylation patterns similar to those seen in human serum in various inflammatory states. IL-1, tumor necrosis factor, and hepatocyte stimulating factor I increased synthesis of ceruloplasmin without alterations in the pattern of its glycosylation. These findings demonstrate that altered glycosylation seen in plasma in some inflammatory states can be explained by the effects of monokines on glycosylation in hepatocytes and that gene expression and glycosylation of some APP during the acute-phase response may be regulated by different mechanisms.

Insulin modulation of acute-phase protein production in a human hepatoma cell line

Cytokine ◽  
1991 ◽  
Vol 3 (6) ◽  
pp. 619-626 ◽  
Author(s):  
Douglas Thompson ◽  
Stephen P. Harrison ◽  
Stuart W. Evans ◽  
John T. Whicher
Keyword(s):  
Cell Line ◽  
Acute Phase ◽  
Protein Production ◽  
Acute Phase Protein ◽  
Hepatoma Cell ◽  
Hepatoma Cell Line ◽  
Human Hepatoma ◽  
Human Hepatoma Cell ◽  
Human Hepatoma Cell Line ◽  
Phase Protein

scholarly journals Effects of dimethyl sulphoxide on the synthesis of plasma proteins in the human hepatoma HepG2. Induction of an acute-phase-like reaction

1988 ◽  
Vol 253 (3) ◽  
pp. 927-930 ◽  
Author(s):  
F Iwasa ◽  
R A Galbraith ◽  
S Sassa
Keyword(s):  
Acute Phase ◽  
Plasma Proteins ◽  
Hepatoma Cell ◽  
Dimethyl Sulphoxide ◽  
Hepatoma Cell Line ◽  
Human Hepatoma ◽  
Human Hepatoma Cell ◽  
Hepatoma Cell Line Hepg2 ◽  
Acute Phase Reactions ◽  
Hepatoma Hepg2

Effects of dimethyl sulphoxide (Me2SO) on the synthesis of plasma proteins by the human hepatoma cell line HepG2 were examined. Me2SO treatment resulted in decreased synthesis of albumin and alpha-fetoprotein, and in increased synthesis of haptoglobin. Plasma-protein profiles induced by Me2SO treatment were very similar to those seen in acute-phase reactions.

scholarly journals The acute-phase response in (NZB X NZW)F1 and MRL/l MICE.

1982 ◽  
Vol 156 (4) ◽  
pp. 1268-1273 ◽  
Author(s):  
C Rordorf ◽  
H P Schnebli ◽  
M L Baltz ◽  
G A Tennent ◽  
M B Pepys
Keyword(s):  
Acute Phase ◽  
Acute Phase Response ◽  
Acute Phase Proteins ◽  
Acute Phase Protein ◽  
Phase Response ◽  
Serum Amyloid ◽  
Human Rheumatoid Arthritis ◽  
Amyloid A ◽  
Serum Amyloid A Protein ◽  
Phase Protein

The acute-phase plasma protein response to disease activity in murine models of autoimmune lupus-like disease was investigated by measurement of the concentration of serum amyloid P component (SAP) in NZB X W and MRL/l mice. The levels of SAP, which is a major acute-phase protein in mice, did not rise at all in response to progression of disease in NZB X W mice between the ages of 1 and 9 mo. This resembles the behavior of acute-phase proteins such as C-reactive protein and serum amyloid A protein in human systemic lupus erythematosus, and just as in human lupus, where the occurrence of intercurrent microbial infection can stimulate an acute-phase response, so injection of bacterial lipopolysaccharide or casein into the NZB X W mice stimulated "normal" acute-phase SAP production. In marked contrast, MRL/l mice developed greatly increased levels of SAP, which correlated closely with progression of their pathology as they aged. The disease profile of the MRL/l strain includes rheumatoid factors and spontaneous polyarthritis and their SAP response resembles the behavior of acute phase proteins in human rheumatoid arthritis. Different patterns of acute-phase response in different autoimmune disorders may thus be a reflection of the genetic predisposition to particular diseases and/or contribute to their pathogenesis. The existence of animal counterparts for the various clinical patterns of human acute-phase protein production will assist in experimental investigation of the underlying mechanisms and of the biological role of the acute-phase response.

Corticotrophin-releasing factor as a mediator of the acute-phase response in rats, mice and rabbits

1993 ◽  
Vol 136 (2) ◽  
pp. 207-216 ◽  
Author(s):  
P. M. Hagan ◽  
S. Poole ◽  
A. F. Bristow
Keyword(s):  
Protein Synthesis ◽  
Acute Phase ◽  
Acute Phase Response ◽  
Acute Phase Proteins ◽  
Acute Phase Protein ◽  
Phase Response ◽  
Interleukin 1Β ◽  
Corticotrophin Releasing Factor ◽  
Phase Protein

ABSTRACT The acute-phase response involves a number of separate physiological components, including induction of acute-phase protein synthesis by the liver. This response can be induced in vivo by administration of the endogenous leucocytic mediator interleukin-1β. A number of in-vivo effects of interleukin-1β have been reported to be mediated by corticotrophin-releasing factor (CRF), including activation of the hypothalamo-pituitary-adrenal axis and induction of fever, and in this report we have examined a possible involvement of CRF in mediating interleukin-1β-induced acute-phase protein synthesis. Interleukin-1β stimulated the elevation of species-specific plasma acute-phase proteins in rats, mice and rabbits. Co-injection of interleukin-1β with the specific CRF receptor antagonist α-helical-CRF9–41 NH2 abolished or attenuated acute-phase protein synthesis induced by interleukin-1β in all three species for up to 12 h after injection. The inhibitory effect of α-helical-CRF9–41NH2 was reduced or absent 24 h after injection. Neutralizing anti-CRF antisera had no effect on acute-phase protein synthesis in the mouse and, paradoxically, potentiated acute-phase protein synthesis induced by interleukin-1β in the rat. These results indicate a possible mediatory role for CRF in regulation of acute-phase protein synthesis, and suggest that CRF may mediate induction of acute-phase protein synthesis by a different mechanism from that involved in regulation of corticotrophin secretion. Journal of Endocrinology (1993) 136, 207–216

scholarly journals Heterogeneous modulation of acute-phase-reactant mRNA levels by interleukin-1 β and interleukin-6 in the human hepatoma cell line PLC/PRF/5

1991 ◽  
Vol 277 (2) ◽  
pp. 477-482 ◽  
Author(s):  
D M Steel ◽  
A S Whitehead
Keyword(s):  
Cell Line ◽  
Acute Phase ◽  
Acute Phase Response ◽  
Hepatoma Cell ◽  
Phase Response ◽  
Serum Amyloid ◽  
Hepatoma Cell Line ◽  
Human Hepatoma ◽  
Human Hepatoma Cell ◽  
Human Hepatoma Cell Line

The acute-phase response to tissue injury and inflammation is accompanied by a dramatic increase in the hepatic synthesis of plasma proteins known as acute-phase reactants (APRs). This response is mediated by cytokines produced in part by activated macrophages at the site of inflammation; glucocorticoids have also been implicated as playing a regulatory role. The effects of the cytokines interleukin (IL)-1 beta and -6, alone or in combination, and in the absence or presence of the synthetic glucocorticoid dexamethasone, on the levels of APR mRNAs in the human hepatoma cell line PLC/PRF/5 were analysed. The accumulation of APR mRNAs [the complement components C3, factor B and Cl inhibitor; the major APRs C-reactive protein (CRP) and serum amyloid A protein and the CRP analogue serum amyloid P protein] was determined in dose-response and time-course studies. The APRs differed from each other in their responses to IL-1 beta alone, IL-6 alone, and IL-1 beta plus IL-6. Dexamethasone enhanced the cytokine-driven induction of a subset of APR mRNAs. These studies detail the heterogeneity of the ‘in vitro’ acute-phase response to defined mediators.

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