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Biomedical subjects

M Hiron

Publications and source records attributed to M Hiron.

29 records · Page 2Linked to original sources
PubMed1990

Partial hepatectomy and mediators of inflammation decrease the expression of liver alpha 2-HS glycoprotein gene in rats.

Liver mRNA levels of two acute phase reactant (APR) proteins, alpha 2-HS glycoprotein (a major negative APR) and alpha 1-acid glycoprotein (a major positive APR) were measured in male rats at different times after the administration of turpentine, of tumor necrosis factor, or following partial hepatectomy. In every case, a marked decrease in mRNA levels of alpha 2-HS glycoprotein was observed which reached a maximum at 24 h. A concomitant increase of alpha 1-acid glycoprotein mRNA levels was observed under the same conditions. These results indicate that the decreased levels of alpha 2-HS glycoprotein induced by the acute-phase response following inflammatory mediators and partial hepatectomy are due to a down-regulation of the gene expression of this protein in rat liver.

Animals↗
PubMed1990

Acute-phase-response induction in rat hepatocytes co-cultured with rat liver epithelial cells.

The response of rat hepatocytes co-cultured with rat liver epithelial cells to conditioned medium (CM) from lipopolysaccharide (LPS)-activated monocytes was investigated by measuring the concentration of alpha 2-macroglobulin (alpha 2M), alpha 1-acid glycoprotein (AGP), albumin and transferrin, as well as the changes in glycosylation of alpha 1-acid glycoprotein. During an initial 8-day treatment with CM, concentrations of alpha 2M and AGP increased markedly over those of control culture, whereas concentrations of albumin and transferrin decreased. The glycosylation pattern of AGP indicated an important relative increase of the concanavalin A-strongly-reactive (SR) variant upon treatment. When CM addition to hepatocyte culture medium was stopped, the concentrations of the four proteins and the glycosylation pattern of AGP reverted to those of control cultures. Further addition (on day 15) to cultures of CM increased the concentration of alpha 2M and decreased albumin and transferrin concentrations. Although AGP concentrations did not increase above those of controls, the appearance of the SR variant was again stimulated by CM. These results show that, in co-culture, rat hepatocytes remain able to respond to repeated inflammatory stimuli.

Albumins↗
PubMed1989

An enzyme-linked immunoassay for the measurement of rat alpha 1-acid glycoprotein synthesized by cultured hepatocytes.

We have developed a sandwich ELISA to quantify rat alpha 1-acid glycoprotein (AGP). The assay correlated well with RID and the minimum detectable concentration was 1 microgram/l. The assay permits high sensitivity determinations of the rate of synthesis of AGP in vitro. The maximum mean rates observed were 1500 and 1800 ng/24 h/10(6) cells for hepatocytes cultured alone and co-cultured hepatocytes respectively and 39 ng/h/10(6) cells for isolated hepatocytes.

Animals↗
PubMed1988

The synthesis of human alpha-2-HS glycoprotein is down-regulated by cytokines in hepatoma HepG2 cells.

The regulation of the synthesis of alpha-2-HS glycoprotein (AHSG) by inflammatory mediators from activated monocytes was studied on the human hepatoma cell line HepG2 and compared to that of albumin. Monocyte-conditioned medium, recombinant human interleukin-6 (rhIL6) and interleukin-1 beta (rhIL1 beta) all down-regulated the synthesis of AHSG. This decrease was found both at the protein and the mRNA level. The most efficient mediator was the monocyte-conditioned medium, when rhIL1 beta was found to be less efficient than rhIL6. The combination of rhIL6 and rhIL1 beta resulted in an additive down-regulation of the AHSG mRNA levels. Similar results were obtained with albumin. These data indicate that AHSG is a negative acute-phase protein whose synthesis is regulated by cytokines in a manner similar to that of albumin.

Blood Proteins↗
PubMed1988

Regulation of alpha 1-acid glycoprotein plasma concentration by sex steroids and adrenal-cortical hormones during experimental inflammation in the rat.

Treatment of adult intact rats with sex steroids (estradiol-17 beta, ethynylestradiol, dihydrotestosterone) raises the concentration of serum acute-phase alpha 1-acid glycoprotein (AGP). Estrogens are more effective than dexamethasone, and experimental inflammation causes an additive effect on AGP synthesis when ethynylestradiol is given simultaneously. Adrenaline is also able to increase the AGP level. Experiments with adrenalectomized and adrenalectomized plus castrated rats result in a 50% reduction in the serum level of AGP as compared with that in normal and hypophysectomized rats. Although ethynylestradiol is the strongest inducer of AGP synthesis in intact animals, it is unable to enhance significantly the AGP level in adrenalectomized rats, contrary to dexamethasone. Adrenalectomized rats are incapable of undergoing a substantial increase in plasma AGP level following experimental inflammation, and ethynylestradiol or adrenaline cannot take the place of dexamethasone in inducing high levels of AGP in these inflamed rats. These results indicate that glucocorticoids play an obligatory role in modulating AGP synthesis either by directly regulating the AGP gene or in modulating AGP synthesis by increasing the stability of AGP mRNA. Finally, it is suggested that glucocorticoids may also act in unmasking receptor binding sites at the AGP gene level for other mediators such as sex steroids and putative inflammatory factors.

Adrenal Cortex Hormones↗
PubMed1986

Long-term biosynthesis of complement component C3 and alpha-1 acid glycoprotein by adult rat hepatocytes in a co-culture system with an epithelial liver cell-type.

We used a system of co-culture of adult rat hepatocytes with another epithelial cell type from rat liver to study the synthesis of two acute-phase reactants, alpha-1 acid glycoprotein (alpha 1AGP) and the third component of complement (C3), and we have obtained long-term secretion of these two proteins. After a period of adaptation corresponding to the first 2-4 days of the co-culture, hepatocytes secreted C3 and alpha 1AGP for at least 2 weeks at a mean level higher than that observed in the first days of a pure culture of hepatocytes. When pulse-chase analysis was performed on day 6 of co-culture, kinetics of synthesis of alpha 1AGP and C3 were the same as those observed on day 1 of a conventional culture of pure hepatocytes. Furthermore, intracellular and extracellular alpha 1AGP had Mr values respectively of 39,000 and of 42,000-52,000, identical with those observed in pure cultures of hepatocytes. Similarly, the molecular size and subunit structures of C3 were the same in co-culture and in cultures, indicating an identical processing of this protein. C3 produced in co-culture was also haemolytically active. Therefore, the system of adult hepatocytes co-cultured with this liver epithelial cell provides a physiological system in vitro which permits long-term synthesis of the two acute-phase reactants C3 and alpha 1AGP. This model opens the possibility to study the modulation of the synthesis of these two proteins during a long period by inflammatory agents or by hormones.

Animals↗
PubMed1985

The effects of 17 alpha-ethynyloestradiol and of acute inflammation on the plasma concentration of rat alpha 1-acid glycoprotein and on the induction of its hepatic mRNA.

We measured the serum concentration of alpha 1-acid glycoprotein (alpha 1-AGP) and we evaluated the content of its hepatic mRNA in rats after 17 alpha-ethynyloestradiol treatment or after turpentine-induced acute inflammation, or after both treatments performed simultaneously. We have also studied the affinity of serum alpha 1-AGP for concanavalin A under these conditions. Both types of stimuli induce a marked retention of the glycoprotein on free concanavalin A. The serum concentration of alpha 1-AGP is increased about 14-fold compared with that in control rats when a single pharmacological dose (50 micrograms) or multiple injections of 17 alpha-ethynyloestradiol are administered. This increase is greater in turpentine-oil-injected rats (about 21-fold) and reaches a maximum (about 32-fold) in rats injected with 17 alpha-ethynyloestradiol plus turpentine oil; this increase in alpha 1-AGP corresponds to the addition of the effects of the two inducing agents. Similar changes are also observed either in the alpha 1-AGP mRNA content as estimated by using an alpha 1-AGP-specific cDNA probe, or in the amount of translatable alpha 1-AGP mRNA. The results indicate that: after a high dose of 17 alpha-ethynyloestradiol and after acute inflammation, the increase of the alpha 1-AGP serum concentration is due to an accumulation of the alpha 1-AGP mRNA; different mechanisms and/or pathways are probably involved in regulating the synthesis of alpha 1-AGP under various stimuli; 17 alpha-ethynyloestradiol as well as acute inflammation seem to control the glycosylation process of alpha 1-AGP in an identical manner.

Animals↗
PubMed1981

Evidence for alpha-1-acid glycoprotein populations of different pI values after concanavalin A affinity chromatography. Study of their evolution during inflammation in man.

Isoelectric focusing in polyacrylamide gel was used to reveal the two alpha 1-acid glycoprotein populations separated by affinity chromatography on Con A-Sepharose from human purified alpha 1-acid glycoprotein, whole normal serum and sera from patients undergoing an acute inflammatory process. The concanavalin A non-reactive peak had a lower isoelectric point than did the concanavalin A reactive peak. Moreover, crossed immunoaffinity electrophoresis with free concanavalin A revealed three alpha 1-acid glycoprotein populations (concanavalin A reactive, weakly and non-reactive). A significant difference was observed between the patterns of normal and of inflammatory sera, since the concanavalin A reactive fraction was enhanced during the inflammatory process. These results suggest a variation in relative ratios of the different types of peripheral oligosaccharide branches in the alpha 1-acid glycoprotein populations.

Chromatography, Affinity↗
PubMedDate not supplied

Interleukin-6 (IL-6) and acute-phase proteins in rats with biliary sepsis.

We measured serum interleukin-6 (IL-6) and acute-phase proteins, alpha 1-acid glycoprotein (AGP) and alpha 2-macroglobulin (alpha 2M), after a retrograde intrabiliary bacterial infection in rats with biliary obstruction. Maximum serum IL-6 was obtained at 6 h in rats following inoculation of bacteria (10(6) CFU/ml E. Coli) in the bile duct and it was higher than that observed in rats undergoing a bile duct ligation or a laparotomy. There was a strict relationship between the level of IL-6 at 6 h and the modified levels of AGP and alpha 2M at 48 h. AGP and alpha 2M levels were the highest in sera of rats with bile duct infection as compared with those found in sera of rats with bile duct ligation or laparotomy. After inoculation of E. Coli or E. Fecalis, blood IL-6 level was always higher at 6 h in inferior vena cava as compared with that found in the supra hepatic vein. These results indicate that IL-6 is synthesized after a biliary sepsis and that its blood level is higher in the systemic circulation than in the local circulation.

Acute-Phase Proteins↗
PubMedDate not supplied

IL-6-induced changes in synthesis of alpha 1-acid glycoprotein in human hepatoma Hep3B cells are distinctively regulated by monoclonal antibodies directed against different epitopes of IL-6 receptor (gp80).

The synthesis of the human acute-phase alpha 1-acid glycoprotein (AGP) is primarily controlled by IL-6 and IL-1 in liver cells. In the present study, monoclonal antibodies against human gp80 interleukin-6 receptor (IL-6R) were utilized to study the role of the IL-6R in the control of the IL-6-induced AGP synthesis in the human hepatoma Hep3B cell line. Two of the 4 MAbs used in this study, M164 and M195, identified 2 different epitopes involved in IL-6 binding and two others, M91 and M182, recognized epitopes not involved in IL-6 binding. Dose-response experiments indicated that up to 55% of AGP synthesis was inhibited by 10(5) ng/ml of MAbs 164 or 195 when Hep3B cells were treated by IL-6 for 48h. Kinetics of the inhibition of AGP synthesis after addition of anti-IL-6R indicated that the decrease of the IL-6-induced AGP synthesis by Hep3B cells was obtained immediately after the addition of the anti-IL-6R MAbs. Of the two MAbs not involved in IL-6 binding, M91 was unable to interfere with the IL-6-induced AGP synthesis whereas, surprisingly, M182 decreased it by about 25%. Since M182 was also able to interfere with the proliferative response of an IL-6 dependent plasma cell line, our results suggested that M182 may be directed to a structure involved in the IL-6/IL-6R gp130 complex formation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗