Glycoprotein biosynthesis during the acute-phase response to inflammation

1983 ◽  
Vol 61 (9) ◽  
pp. 1041-1048 ◽  
Author(s):  
J. C. Jamieson ◽  
H. A. Kaplan ◽  
B. M. R. N. J. Woloski ◽  
M. Hellman ◽  
K. Ham

Inflammation results in an increase in the levels of a variety of glycoproteins in serum. The glycoproteins that respond in this way are usually referred to as acute-phase reactants. Studies on the acute-phase response of rat α1-acid glycoprotein showed that there was an increase in the liver levels of this glycoprotein at 12 h after turpentine inflammation. This was followed by increased serum levels at 48–72 h after inflammation, suggesting a precursor–product relationship between liver and serum α1-acid glycoprotein. Incorporation studies coupled with measurements of synthesis rates of α1-acid glycoprotein showed that increased synthesis was responsible for the acute-phase response of this protein to inflammation. These studies also showed that albumin was a negative acute-phase reactant. The acute-phase response of α1-acid glycoprotein was accompanied by increased liver pools of UDP–N-acetylglucosamine (UDP–GlcNAc) and UDP–N-acetylgalactosamine (UDP–GalNAc) and increased liver activities of glucosamine-6-phosphate synthase and UDP–GlcNAc 2-epimerase. Activities of galactosyl and sialyl transferases in liver were also elevated and serum sialyl transferase was increased substantially in inflammation, suggesting that it may also be an acute-phase reactant. Liver activities of β-N-acetylhexosaminidase and β-galactosidase declined by about 50% at 24 h after inflammation; there was evidence that serum levels of these enzymes increased at 24–72 h after inflammation, suggesting that the lysosomal glycosidases may be released from liver during inflammation. Inflammation resulted in elevated serum Cortisol, insulin, and adrenocorticotropic hormone and induced increased glycogenosis; liver cAMP levels were also increased during inflammation. Preliminary studies are presented to show that leukocyte-derived factors may be involved in the acute-phase response of α1-acid glycoprotein to inflammation.

1997 ◽  
Vol 273 (6) ◽  
pp. R1998-R2004 ◽  
Author(s):  
Terrence Deak ◽  
Jennifer L. Meriwether ◽  
Monika Fleshner ◽  
Robert L. Spencer ◽  
Amer Abouhamze ◽  
...  

Exposing rats to a single session of inescapable tail shock (IS) reduces corticosteroid binding globulin (CBG) 24 h later (Fleshner et al., Endocrinology 136: 5336–5342, 1995). The present experiments examined whether reductions in CBG are differentially affected by controllable vs. identical uncontrollable tail shock, are mediated by IS-induced glucocorticoid elevation, or reflect IS-induced activation of the acute phase response and whether IS produces fever. The results demonstrate that 1) equivalent reductions in CBG are observed in response to escapable tail shock or yoked IS, 2) IS-induced CBG reduction is not blocked by adrenalectomy in rats that receive basal corticosteroid replacement or by pretreatment with RU-38486, and 3) IS appears to activate the acute phase response, since IS reduces serum levels of an acute-phase negative reactant (CBG), increases serum levels of acute-phase positive reactants (haptoglobin and α1-acid glycoprotein), and increases core body temperature 20–24 h later.


1995 ◽  
Vol 268 (6) ◽  
pp. R1507-R1512 ◽  
Author(s):  
H. K. Srere ◽  
D. Belke ◽  
L. C. Wang ◽  
S. L. Martin

alpha 2-Macroglobulin, a major acute phase reactant in many species, increases in the Richardson's ground squirrel (Spermophilus richarsonii) during hibernation at the level of both mRNA and protein. To determine if the pattern of liver gene expression known as the acute phase response is elicited as a normal part of the physiological adaptation of hibernation, acute phase reactants were identified in the Richardson's ground squirrel and were then assayed for changes in mRNA expression in the livers of active and hibernating ground squirrels. Our data demonstrate that alpha 1-antitrypsin, alpha 2-macroglobulin, ceruloplasmin, C-reactive protein, and serum amyloid A are acute phase reactants in the Richardson's ground squirrel. Of these, only alpha 2-macroglobulin (alpha 2M) mRNA increases during hibernation, demonstrating that the entire acute phase response is not elicited as a part of the adaptation for hibernation. Alternatively, data from blood clotting assays of serum from active and hibernating animals support a role for the increase in alpha 2M protein during hibernation in decreasing the coagulative properties of the blood.


2010 ◽  
Vol 24 (2) ◽  
pp. 391-401 ◽  
Author(s):  
Sutapa Ray ◽  
Chang Lee ◽  
Tieying Hou ◽  
Kishor K. Bhakat ◽  
Allan R. Brasier

Abstract The signal transducer and activator of transcription-3 (STAT3) is a latent IL-6 inducible transcription factor that mediates hepatic and vascular inflammation. In this study, we make the novel observation that STAT3 forms an inducible complex with the apurinic/apyrimidinic endonuclease 1 (APE1)/redox effector factor-1 (APE1/Ref-1), an essential multifunctional protein in DNA base excision repair, and studied the role of APE1/Ref-1 in STAT3 function. Using a transfection-coimmunoprecipitation assay, we observed that APE1 selectively binds the NH2-terminal acetylation domain of STAT3. Ectopic expression of APE1 potentiated inducible STAT3 reporter activity, whereas knockdown of APE1 resulted in reduced IL-6-inducible acute-phase reactant protein expression (C-reactive protein and serum amyloid P) and monocyte chemotactic protein-1 expression. The mechanism for APE1 requirement in IL-6 signaling was indicated by reduced STAT3 DNA binding activity observed in response to small interfering RNA-mediated APE1 silencing. Consistent with these in vitro studies, we also observed that lipopolysaccharide-induced activation of acute-phase reactant protein expression is significantly abrogated in APE1 heterozygous mice compared with wild-type mice. IL-6 induces both STAT3 and APE1 to bind the suppressor of cytokine signaling-3 and γ-fibrionogen promoters in their native chromatin environment. Moreover, we observed that APE1 knockdown destabilized formation of the STAT3-inducible enhanceosome on the endogenous γ-fibrionogen promoter. Taken together, our study indicates that IL-6 induces a novel STAT3-APE1 complex, whose interaction is required for stable chromatin association in the IL-6-induced hepatic acute phase response.


2011 ◽  
Author(s):  
Kellen C. K. Barbosa ◽  
Daniel F. Cunha ◽  
Alceu A. Jordão Jr. ◽  
Virgínia R. S. Weffort ◽  
Selma F. C. Cunha

1989 ◽  
Vol 170 (1) ◽  
pp. 349-354 ◽  
Author(s):  
D Bernuau ◽  
L Legrès ◽  
Y Lamri ◽  
N Giuily ◽  
G Fey ◽  
...  

Functional heterogeneity in the lobule with regard to plasma protein synthesis is still debated. Therefore, we have localized in liver sections from normal rats and from rats with turpentine-induced AIR the mRNA and protein products of three genes with different alterations in their hepatic expression during an AIR: alpha 2M and alpha 1PI, two positively reacting acute-phase genes, and alpha 1I3, a negative acute-phase reactant. In normal liver, all hepatocytes expressed alpha 2M and alpha 1I3 mRNA, but a preferential expression of alpha 2M and alpha 1I3 mRNA and protein in the PP and ML zones was observed. During an AIR, the level of alpha 2M mRNA increased fourfold in the cytoplasm of PP and ML hepatocytes, while the level of cytoplasmic alpha 1I3 mRNA was decreased about fourfold in the same zones, with parallel variations in the expression of the corresponding proteins. In contrast, no significant modulation of the RNA and protein concentrations of both genes was detected in PV areas. alpha 1PI mRNA was expressed at the same levels in the three lobular zones in normal liver, but staining for the alpha 1PI protein was more intense in the PV zones. During the acute-phase response alpha 1PI mRNA levels were increased twofold in all three lobular zones, and alpha 1PI staining became homogeneous within the lobule. These results demonstrate that the location of a hepatocyte with the liver lobule can influence the expression of the three genes under study both at pre- and post-translational levels, in basal conditions, as well as during modulation of their expression during the inflammatory reaction.


1990 ◽  
Vol 68 (21) ◽  
pp. 1083-1083 ◽  
Author(s):  
H. Tilg ◽  
J. Mair ◽  
M. Herold ◽  
W. E. Aulitzky ◽  
P. Lechleitner ◽  
...  

2009 ◽  
Vol 28 (2) ◽  
pp. 116-121 ◽  
Author(s):  
Irena Kafeđiska ◽  
Dejan Spasovski ◽  
Todor Gruev ◽  
Mane Grličkov ◽  
Kočo Cakalaroski ◽  
...  

Association Between Osteoarticular Scores and Acute Phase Reactant Levels in Rheumatoid Arthritis The aim of this prospective control study was a quantitative evaluation of the activity of rheumatoid arthritis (RA) in certain time intervals, using articular indexes (set of 28 sensitive and 28 swollen joints), laboratory parameters (Hb, Hct, Er, Le and Plt) and acute phase reactants (ESR, RF, CRP); to determine which of the acute phase reactants is the most useful biochemical marker for the evaluation of disease activity in RA; to quantify the therapeutical and laboratory differences in certain time intervals in the group with and without immunomodulatory therapy with Methotrexate. Sixty patients with RA were included, 27 of who were treated with non-steroid antiinflammatory drugs (NSAIDs) and Methotrexate (MTX). The control group consisted of 33 patients treated only with NSAIDs because of irregular controls. In the first group of patients the disease activity was estimated at four time intervals, and in the control group of patients at three time intervals following the scores of the articular indexes, blood cell counts, ESR and CRP in every patient. In the first group of patients decreased activity of RA was found upon every following control with a consecutive decrease in mean values of the scores of articular indexes with statistically significant differences at the four time intervals. Considering laboratory parameters, there were statistically significant differences in the mean values of Hb, Er, Plt, ESR, (p=0.0462, p=0.0076, p= 0.0058, p= 0.0003). Mean values of CRP did not show statistically significant differences, but the number of patients who were CRP negative increased (there were great standard deviations). In the group of patients treated only with NSAIDs, there were statistically significant differences in the mean values of the scores of articular indexes with an increse at every following control (in favour of progression of the disease). There were no statistically significant differences considering blood cell counts, ESR and CRP (in favour of permanently active disease). In conclusion, CRP is the most useful marker for the prospective follow-up of patients with RA.


Surgery ◽  
1996 ◽  
Vol 119 (6) ◽  
pp. 664-673 ◽  
Author(s):  
David A. Gilpin ◽  
Ching-Chyuan Hsieh ◽  
David T. Kuninger ◽  
David N. Herndon ◽  
John Papaconstantinou

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