scholarly journals Pretranslational modulation of acute phase hepatic protein synthesis by murine recombinant interleukin 1 (IL-1) and purified human IL-1.

1985 ◽  
Vol 162 (3) ◽  
pp. 930-942 ◽  
Author(s):  
G Ramadori ◽  
J D Sipe ◽  
C A Dinarello ◽  
S B Mizel ◽  
H R Colten
Keyword(s):  
Gene Expression ◽  
Acute Phase ◽  
Acute Phase Response ◽  
Messenger Rna ◽  
Tissue Injury ◽  
Interleukin 1 ◽  
Phase Response ◽  
Complement Factor ◽  
Factor B ◽  
Amyloid A

During the acute phase response to tissue injury or inflammation, the concentration of several plasma proteins change. Previous work (29-34) suggested a role for interleukin 1 (IL-1) in the acute phase response. The availability of recombinant-generated mouse IL-1 prompted a study designed to directly test the function of IL-1 and its mechanism of action on hepatic synthesis of two positive acute phase proteins (serum amyloid A [SAA] and complement factor B), and a negative acute phase reactant (albumin). Intravenous injection of purified recombinant-generated murine-IL-1 into C3H/HeJ endotoxin-resistant mice induced a dose-dependent increase in SAA-specific hepatic messenger RNA (mRNA), and an increase in SAA plasma protein concentration. In primary murine hepatocyte cultures, both the recombinant IL-1 and highly purified human IL-1 induced a dose- and time-dependent, reversible increase in expression of the SAA and factor B genes, and a decrease in albumin gene expression. This regulation is pretranslational, since the kinetics and direction of change in specific mRNA for SAA, factor B, and albumin correspond to the changes in synthesis of the respective proteins. Moreover, the effect of IL-1 was specific, since actin gene expression was unaffected, and the IL-1 response was inhibited by antibody specific for IL-1. These data provide direct evidence that a single mediator, IL-1, can effect the positive and negative changes in specific hepatic gene expression characteristic of the acute phase response.

alpha 2-Macroglobulin gene expression during hibernation in ground squirrels is independent of acute phase response

1995 ◽  
Vol 268 (6) ◽  
pp. R1507-R1512 ◽  
Author(s):  
H. K. Srere ◽  
D. Belke ◽  
L. C. Wang ◽  
S. L. Martin
Keyword(s):  
Gene Expression ◽  
Acute Phase ◽  
Acute Phase Response ◽  
Ground Squirrel ◽  
Acute Phase Reactant ◽  
Ground Squirrels ◽  
Phase Response ◽  
Physiological Adaptation ◽  
Acute Phase Reactants ◽  
Amyloid A

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.

The acute phase response and C-reactive protein

2020 ◽  
pp. 2199-2207
Author(s):  
Mark B. Pepys
Keyword(s):  
Acute Phase ◽  
Acute Phase Response ◽  
Serum Amyloid A ◽  
Acute Phase Proteins ◽  
Phase Response ◽  
Serum Amyloid ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Amyloid A ◽  
Serum Amyloid A Protein

The acute phase response—trauma, tissue necrosis, infection, inflammation, and malignant neoplasia induce a complex series of nonspecific systemic, physiological, and metabolic responses including fever, leucocytosis, catabolism of muscle proteins, greatly increased de novo synthesis and secretion of a number of ‘acute phase’ plasma proteins, and decreased synthesis of albumin, transthyretin, and high- and low-density lipoproteins. The altered plasma protein concentration profile is called the acute phase response. Acute phase proteins—these are mostly synthesized by hepatocytes, in which transcription is controlled by cytokines including interleukin 1, interleukin 6, and tumour necrosis factor. The circulating concentrations of complement proteins and clotting factors increase by up to 50 to 100%; some of the proteinase inhibitors and α‎1-acid glycoprotein can increase three- to fivefold; but C-reactive protein (CRP) and serum amyloid A protein (an apolipoprotein of high-density lipoprotein particles) are unique in that their concentrations can change by more than 1000-fold. C-reactive protein—this consists of five identical, nonglycosylated, noncovalently associated polypeptide subunits. It binds to autologous and extrinsic materials which contain phosphocholine, including bacteria and their products. Ligand-bound CRP activates the classical complement pathway and triggers the inflammatory and opsonizing activities of the complement system, thereby contributing to innate host resistance to pneumococci and probably to recognition and safe ‘scavenging’ of cellular debris. Clinical features—(1) determination of CRP in serum or plasma is the most useful marker of the acute phase response in most inflammatory and tissue damaging conditions. (2) Acute phase proteins may be harmful in some circumstances. Sustained increased production of serum amyloid A protein can lead to the deposition of AA-type, reactive systemic amyloid.

Interleukin 1-induced depression of iron and zinc: role of granulocytes and lactoferrin

1987 ◽  
Vol 252 (1) ◽  
pp. E27-E32 ◽  
Author(s):  
S. E. Goldblum ◽  
D. A. Cohen ◽  
M. Jay ◽  
C. J. McClain
Keyword(s):  
Acute Phase ◽  
Acute Phase Response ◽  
Interleukin 1 ◽  
Phase Response ◽  
Human Transferrin ◽  
Carrier Molecule ◽  
Iron And Zinc

The mechanism(s) of stress-induced hypoferremia and hypozincemia remains unclear. We studied the role of granulocytes and lactoferrin (LF) in endotoxin and murine interleukin 1 (IL-1)-induced depression of serum Fe and Zn concentrations in both rabbits and rats. Both endotoxin and IL-1 administration induced significant hypoferremia (P less than 0.01) and hypozincemia (P less than 0.01) after 6 h in both species. Granulocyte depletion before IL-1 infusion significantly (P less than 0.01) diminished the hypoferremia but not the hypozincemia. Moreover, infusion of 5 or 15 mg of human LF into rabbits caused significant hypoferremia (P less than 0.005) without hypozincemia. Significant hypozincemia (P less than 0.01) could only be demonstrated after a 75-mg infusion. In contrast, infusions of human transferrin at equivalent doses (5, 15, and 75 mg) induced neither hypoferremia nor hypozincemia. Therefore endotoxin and IL-1-induced hypoferremia and, to a much lesser degree, hypozincemia are granulocyte dependent. Granulocyte released LF is a specific carrier molecule for transport and removal of Fe from the circulation during the acute phase response. The data suggest a mechanistic dissociation of IL-1-induced hypoferremia and hypozincemia with LF-independent mechanisms for Zn.

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