Skip to main content
NCBI home page
Mediators of Inflammation logoLink to Mediators of Inflammation
. 1996 Sep;5(4):266–270. doi: 10.1155/S0962935196000385

α2-macroglobulin and α1-inhibitor-3 mRNA expression in the rat liver after slow interleukin-1 stimulation

T Gudmundsson 1,✉, P Björk 1, K Ohlsson 1
PMCID: PMC2365808  PMID: 18475738

Abstract

In this study we have investigated total fiver RNA and the expression of mRNA in the rat fiver in vivo after a slow stimulation of interleukin-1. A total dose of 4 μg interleukin-1β was administered via a subcutaneously implanted osmotic minipump over a period of 7 days. Plasma concentrations of α2-macroglobulin manifested a rapid increase, reaching a peak on day 2, while α1-inhibitor-3 manifested a marked initial decrease to 50% of the baseline level, followed by a tendency to increase again. For measurement of total RNA and specific mRNAs from the fiver, rats were sacrificed at different times during the experimental period. Total RNA peaked at 6 h, the level being approximately 60% higher than baseline value. Specific mRNA from the liver for α2-macroglobulin and α1-inhibitor-3 were quantified using laser densitometry on slot blots. The amounts measured during the experimental period agreed with the pattern of corresponding plasma protein levels. From barely detectable amounts at baseline, α2-macroglobulin mRNA peaked on day 1, and then declined. Levels of α1-inhibitor-3 mRNA manifested an initial increase at 3 h, but then declined and remained low until day 5 when there was a tendency towards an increase. It was concluded that the levels of plasma concentrations of α2-macroglobulin and α1-inhibitor-3 are mainly regulated at the protein synthesis level, and that long-term interleukin-1β release could not override the initial acute phase protein counteracting mechanism triggered.

Full Text

The Full Text of this article is available as a PDF (475.3 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aiello L. P., Shia M. A., Robinson G. S., Pilch P. F., Farmer S. R. Characterization and hepatic expression of rat alpha 1-inhibitor III mRNA. J Biol Chem. 1988 Mar 15;263(8):4013–4022. [PubMed] [Google Scholar]
  2. Baumann H., Gauldie J. Regulation of hepatic acute phase plasma protein genes by hepatocyte stimulating factors and other mediators of inflammation. Mol Biol Med. 1990 Apr;7(2):147–159. [PubMed] [Google Scholar]
  3. Bjrök P., Ohlsson K. The interleukin-1 receptor antagonist influences interleukin-1 effects in rat and mouse. Mediators Inflamm. 1992;1(1):27–31. doi: 10.1155/S0962935192000061. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Björk P., Gudmundsson T., Ohlsson K. Acute phase protein response and polymorphonuclear leukocyte cathepsin g release after slow interleukin-1 stimulation in the rat. Mediators Inflamm. 1994;3(6):425–431. doi: 10.1155/S0962935194000608. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Braciak T. A., Northemann W., Hudson G. O., Shiels B. R., Gehring M. R., Fey G. H. Sequence and acute phase regulation of rat alpha 1-inhibitor III messenger RNA. J Biol Chem. 1988 Mar 15;263(8):3999–4012. [PubMed] [Google Scholar]
  6. Colotta F., Dower S. K., Sims J. E., Mantovani A. The type II 'decoy' receptor: a novel regulatory pathway for interleukin 1. Immunol Today. 1994 Dec;15(12):562–566. doi: 10.1016/0167-5699(94)90217-8. [DOI] [PubMed] [Google Scholar]
  7. Colotta F., Re F., Muzio M., Polentarutti N., Minty A., Caput D., Ferrara P., Mantovani A. Interleukin-13 induces expression and release of interleukin-1 decoy receptor in human polymorphonuclear cells. J Biol Chem. 1994 Apr 29;269(17):12403–12406. [PubMed] [Google Scholar]
  8. Demczuk S., Chandler A. M. Changes in hepatic RNA, poly(A)+RNA, and poly(A)-RNA during the acute phase response to inflammation. Biochem Int. 1986 Jan;12(1):155–165. [PubMed] [Google Scholar]
  9. Falkenberg C., Grubb A., Akerström B. Isolation of rat serum alpha 1-microglobulin. Identification of a complex with alpha 1-inhibitor-3, a rat alpha 2-macroglobulin homologue. J Biol Chem. 1990 Sep 25;265(27):16150–16157. [PubMed] [Google Scholar]
  10. Gauthier F., Mouray H. Rat alpha2 acute-phase macroglobulin. Isolation and physicochemical properties. Biochem J. 1976 Dec 1;159(3):661–665. doi: 10.1042/bj1590661. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gauthier F., Ohlsson K. Isolation and some properties of a new enzyme-binding protein in rat plasma. Hoppe Seylers Z Physiol Chem. 1978 Aug;359(8):987–992. doi: 10.1515/bchm2.1978.359.2.987. [DOI] [PubMed] [Google Scholar]
  12. Gehring M. R., Shiels B. R., Northemann W., de Bruijn M. H., Kan C. C., Chain A. C., Noonan D. J., Fey G. H. Sequence of rat liver alpha 2-macroglobulin and acute phase control of its messenger RNA. J Biol Chem. 1987 Jan 5;262(1):446–454. [PubMed] [Google Scholar]
  13. Granowitz E. V., Clark B. D., Mancilla J., Dinarello C. A. Interleukin-1 receptor antagonist competitively inhibits the binding of interleukin-1 to the type II interleukin-1 receptor. J Biol Chem. 1991 Aug 5;266(22):14147–14150. [PubMed] [Google Scholar]
  14. Hannum C. H., Wilcox C. J., Arend W. P., Joslin F. G., Dripps D. J., Heimdal P. L., Armes L. G., Sommer A., Eisenberg S. P., Thompson R. C. Interleukin-1 receptor antagonist activity of a human interleukin-1 inhibitor. Nature. 1990 Jan 25;343(6256):336–340. doi: 10.1038/343336a0. [DOI] [PubMed] [Google Scholar]
  15. Koj A., Magielska-Zero D., Kurdowska A., Bereta J. Proteinase inhibitors as acute phase reactants: regulation of synthesis and turnover. Adv Exp Med Biol. 1988;240:171–181. doi: 10.1007/978-1-4613-1057-0_21. [DOI] [PubMed] [Google Scholar]
  16. Laurell C. B. Electroimmuno assay. Scand J Clin Lab Invest Suppl. 1972;124:21–37. doi: 10.3109/00365517209102748. [DOI] [PubMed] [Google Scholar]
  17. Lonberg-Holm K., Reed D. L., Roberts R. C., Hebert R. R., Hillman M. C., Kutney R. M. Three high molecular weight protease inhibitors of rat plasma. Isolation, characterization, and acute phase changes. J Biol Chem. 1987 Jan 5;262(1):438–445. [PubMed] [Google Scholar]
  18. Ohlsson K., Björk P., Bergenfeldt M., Hageman R., Thompson R. C. Interleukin-1 receptor antagonist reduces mortality from endotoxin shock. Nature. 1990 Dec 6;348(6301):550–552. doi: 10.1038/348550a0. [DOI] [PubMed] [Google Scholar]
  19. Schweizer M., Takabayashi K., Geiger T., Laux T., Biermann G., Buhler J. M., Gauthier F., Roberts L. M., Heinrich P. C. Identification and sequencing of cDNA clones for the rodent negative acute-phase protein alpha 1-inhibitor 3. Eur J Biochem. 1987 Apr 15;164(2):375–381. doi: 10.1111/j.1432-1033.1987.tb11068.x. [DOI] [PubMed] [Google Scholar]
  20. Strohman R. C., Moss P. S., Micou-Eastwood J., Spector D., Przybyla A., Paterson B. Messenger RNA for myosin polypeptides: isolation from single myogenic cell cultures. Cell. 1977 Feb;10(2):265–273. doi: 10.1016/0092-8674(77)90220-3. [DOI] [PubMed] [Google Scholar]
  21. Tilg H., Trehu E., Atkins M. B., Dinarello C. A., Mier J. W. Interleukin-6 (IL-6) as an anti-inflammatory cytokine: induction of circulating IL-1 receptor antagonist and soluble tumor necrosis factor receptor p55. Blood. 1994 Jan 1;83(1):113–118. [PubMed] [Google Scholar]

Articles from Mediators of Inflammation are provided here courtesy of Wiley

RESOURCES