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Influence of chronic inflammation on the level of mRNA for acute-phase reactants in the mouse liver
Abstract:
Systemic injuries provoke a coordinate change in the hepatic synthesis and circulating concentration of plasma proteins. To assess the effect of a transition from acute to chronic inflammation on the expression of the plasma protein genes, the qualitative and quantitative changes of liver mRNA were measured in males of the inbred strain C57BL/6 of Mus musculus during a 14-day period of inflammation. Inflammation was induced and maintained by repeated injections of the irritants, turpentine, lipopolysaccharides, and celite. At various times, total RNA was extracted from the liver. The concentration of specific mRNA was quantitated by cellfree translation and by blot hybridization with cDNA. The mRNA for the increased plasma proteins serum amyloid A, alpha 1-acid glycoprotein, haptoglobin, and alpha-fibrinogen showed essentially the same time course of changes. The concentrations were maximal 24 hr after initiation of inflammation and then declined gradually during the following days. During the progression from acute to chronic inflammation, there was a switch from a predominant expression of the gene for alpha 1-acid glycoprotein-1 to one of alpha 1-acid glycoprotein-2. The prolonged inflammation had an inverse effect on the two major negative acute-phase reactants, albumin and major urinary proteins. The concentration of albumin mRNA was reduced to 50% after 24 hr of inflammation but returned to the control level within 5 days. The mRNA for major urinary proteins, however, were lowered within 2 to 5 days of inflammation to 10 to 20% and were maintained at that level. These results suggest that different regulatory factors, humoral and/or cellular, are involved in controlling the expression of the genes for positive and negative acute-phase plasma proteins during acute and chronic inflammation.
Insights
This study tracked liver gene expression during inflammation in mice. Acute inflammation initially boosted some protein genes, but chronic inflammation shifted gene expression and reduced others, indicating complex regulatory responses.
Area of Science:
- Biochemistry
- Molecular Biology
- Immunology
Background:
- Systemic injuries alter hepatic synthesis and circulating concentrations of plasma proteins.
- Understanding the transition from acute to chronic inflammation is crucial for comprehending gene expression changes.
Purpose of the Study:
- To investigate the qualitative and quantitative changes in liver messenger RNA (mRNA) during a 14-day inflammatory period.
- To assess the effect of acute to chronic inflammation on plasma protein gene expression.
Main Methods:
- Induced and maintained inflammation in C57BL/6 mice using turpentine, lipopolysaccharides, and celite.
- Extracted total RNA from liver tissue at various time points.
- Quantitated specific mRNA concentrations using cell-free translation and blot hybridization with cDNA.
Main Results:
- mRNA for positive acute-phase proteins (serum amyloid A, alpha 1-acid glycoprotein, haptoglobin, alpha-fibrinogen) peaked at 24 hours and then declined.
- A shift in alpha 1-acid glycoprotein gene expression occurred from A1 to A2 during the progression from acute to chronic inflammation.
- Albumin mRNA levels decreased by 50% at 24 hours but recovered within 5 days, while major urinary protein mRNA levels dropped to 10-20% and remained suppressed.
Conclusions:
- Different regulatory factors control the expression of positive and negative acute-phase plasma protein genes during inflammation.
- The transition from acute to chronic inflammation involves distinct regulatory mechanisms affecting gene expression patterns.