Skip to main content
PMC home page
Biochemical Journal logoLink to Biochemical Journal
. 1990 Nov 1;271(3):827–830. doi: 10.1042/bj2710827

Interleukin-1 beta prevents the stimulatory effect of transforming growth factor-beta on collagen gene expression in human skin fibroblasts.

J Heino 1, T Heinonen 1
PMCID: PMC1149639  PMID: 2244882

Abstract

Transforming growth factors beta 1 and beta 2 (TGF-beta 1 and TGF-beta 2) are well-characterized strong inducers of collagen gene expression. A 100 pM concentration of TGF-beta 1 or TGF-beta 2 increases pro alpha 1(I) collagen mRNA levels in human skin fibroblasts 6.6-fold and 7.0-fold respectively, and also increases the accumulation of procollagens in the cell culture medium. Interleukin-1 beta (IL-1 beta) is an inflammatory mediator which also regulates connective tissue metabolism. A small concentration of IL-1 beta (0.01-1.0 unit/ml) slightly increases pro alpha 1(I) collagen mRNA levels (2.2-fold). Here we provide evidence that IL-1 beta prevents the stimulatory effect of TGFs-beta on collagen synthesis in human skin fibroblasts. An IL-1 beta concentration of 1 unit/ml is enough to keep pro alpha 1(I) collagen mRNA levels at control values in cells stimulated by 100 pM-TGF-beta 1. Thus the results indicate that IL-1 beta inhibits collagen synthesis in cells activated by TGFs-beta, whereas it does not significantly change or might even stimulate collagen gene expression in non-activated cells.

Full text

PDF
827

Images in this article

828Fig. 1.
on p.828
828Fig. 2.
on p.828

Selected References

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

  1. Andrews H. J., Edwards T. A., Cawston T. E., Hazleman B. L. Transforming growth factor-beta causes partial inhibition of interleukin 1-stimulated cartilage degradation in vitro. Biochem Biophys Res Commun. 1989 Jul 14;162(1):144–150. doi: 10.1016/0006-291x(89)91974-8. [DOI] [PubMed] [Google Scholar]
  2. Bassols A., Massagué J. Transforming growth factor beta regulates the expression and structure of extracellular matrix chondroitin/dermatan sulfate proteoglycans. J Biol Chem. 1988 Feb 25;263(6):3039–3045. [PubMed] [Google Scholar]
  3. Chandrasekhar S., Harvey A. K. Transforming growth factor-beta is a potent inhibitor of IL-1 induced protease activity and cartilage proteoglycan degradation. Biochem Biophys Res Commun. 1988 Dec 30;157(3):1352–1359. doi: 10.1016/s0006-291x(88)81024-6. [DOI] [PubMed] [Google Scholar]
  4. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  5. Dinarello C. A. Biology of interleukin 1. FASEB J. 1988 Feb;2(2):108–115. [PubMed] [Google Scholar]
  6. Duncan M. R., Berman B. Differential regulation of collagen, glycosaminoglycan, fibronectin, and collagenase activity production in cultured human adult dermal fibroblasts by interleukin 1-alpha and beta and tumor necrosis factor-alpha and beta. J Invest Dermatol. 1989 May;92(5):699–706. doi: 10.1111/1523-1747.ep12696891. [DOI] [PubMed] [Google Scholar]
  7. Edwards D. R., Murphy G., Reynolds J. J., Whitham S. E., Docherty A. J., Angel P., Heath J. K. Transforming growth factor beta modulates the expression of collagenase and metalloproteinase inhibitor. EMBO J. 1987 Jul;6(7):1899–1904. doi: 10.1002/j.1460-2075.1987.tb02449.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fort P., Marty L., Piechaczyk M., el Sabrouty S., Dani C., Jeanteur P., Blanchard J. M. Various rat adult tissues express only one major mRNA species from the glyceraldehyde-3-phosphate-dehydrogenase multigenic family. Nucleic Acids Res. 1985 Mar 11;13(5):1431–1442. doi: 10.1093/nar/13.5.1431. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Goldring M. B., Krane S. M. Modulation by recombinant interleukin 1 of synthesis of types I and III collagens and associated procollagen mRNA levels in cultured human cells. J Biol Chem. 1987 Dec 5;262(34):16724–16729. [PubMed] [Google Scholar]
  10. Harrison J. R., Vargas S. J., Petersen D. N., Lorenzo J. A., Kream B. E. Interleukin-1 alpha and phorbol ester inhibit collagen synthesis in osteoblastic MC3T3-E1 cells by a transcriptional mechanism. Mol Endocrinol. 1990 Feb;4(2):184–190. doi: 10.1210/mend-4-2-184. [DOI] [PubMed] [Google Scholar]
  11. Heino J. Connective tissue components in synovial fibroblast cultures exposed to interleukin 1 and prostaglandin E2. Virchows Arch B Cell Pathol Incl Mol Pathol. 1986;50(4):313–320. doi: 10.1007/BF02889910. [DOI] [PubMed] [Google Scholar]
  12. Heino J., Ignotz R. A., Hemler M. E., Crouse C., Massagué J. Regulation of cell adhesion receptors by transforming growth factor-beta. Concomitant regulation of integrins that share a common beta 1 subunit. J Biol Chem. 1989 Jan 5;264(1):380–388. [PubMed] [Google Scholar]
  13. Heino J., Kähäri V. M., Mauviel A., Krusius T. Human recombinant interleukin-1 regulates cellular mRNA levels of dermatan sulphate proteoglycan core protein. Biochem J. 1988 May 15;252(1):309–312. doi: 10.1042/bj2520309. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Heino J., Massagué J. Cell adhesion to collagen and decreased myogenic gene expression implicated in the control of myogenesis by transforming growth factor beta. J Biol Chem. 1990 Jun 25;265(18):10181–10184. [PubMed] [Google Scholar]
  15. Heino J., Massagué J. Transforming growth factor-beta switches the pattern of integrins expressed in MG-63 human osteosarcoma cells and causes a selective loss of cell adhesion to laminin. J Biol Chem. 1989 Dec 25;264(36):21806–21811. [PubMed] [Google Scholar]
  16. Hynes R. O. Integrins: a family of cell surface receptors. Cell. 1987 Feb 27;48(4):549–554. doi: 10.1016/0092-8674(87)90233-9. [DOI] [PubMed] [Google Scholar]
  17. Ignotz R. A., Heino J., Massagué J. Regulation of cell adhesion receptors by transforming growth factor-beta. Regulation of vitronectin receptor and LFA-1. J Biol Chem. 1989 Jan 5;264(1):389–392. [PubMed] [Google Scholar]
  18. Ignotz R. A., Massagué J. Transforming growth factor-beta stimulates the expression of fibronectin and collagen and their incorporation into the extracellular matrix. J Biol Chem. 1986 Mar 25;261(9):4337–4345. [PubMed] [Google Scholar]
  19. Ingber D. E., Folkman J. How does extracellular matrix control capillary morphogenesis? Cell. 1989 Sep 8;58(5):803–805. doi: 10.1016/0092-8674(89)90928-8. [DOI] [PubMed] [Google Scholar]
  20. Jalkanen M., Tammi M., Vihersaari T., Peltonen J., Kulonen E., Penttinen R. A rapid assay to measure collagen synthesis in cell cultures. J Biochem Biophys Methods. 1980 Jun;2(6):331–339. doi: 10.1016/s0165-022x(80)90050-0. [DOI] [PubMed] [Google Scholar]
  21. Juva K., Prockop D. J. Modified procedure for the assay of H-3-or C-14-labeled hydroxyproline. Anal Biochem. 1966 Apr;15(1):77–83. doi: 10.1016/0003-2697(66)90249-1. [DOI] [PubMed] [Google Scholar]
  22. Kähäri V. M., Heino J., Vuorio E. Interleukin-1 increases collagen production and mRNA levels in cultured skin fibroblasts. Biochim Biophys Acta. 1987 Jul 6;929(2):142–147. doi: 10.1016/0167-4889(87)90169-8. [DOI] [PubMed] [Google Scholar]
  23. Laato M., Heino J. Interleukin 1 modulates collagen accumulation by rat granulation tissue cells both in vivo and in vitro. Experientia. 1988 Jan 15;44(1):32–34. doi: 10.1007/BF01960234. [DOI] [PubMed] [Google Scholar]
  24. Lafyatis R., Thompson N. L., Remmers E. F., Flanders K. C., Roche N. S., Kim S. J., Case J. P., Sporn M. B., Roberts A. B., Wilder R. L. Transforming growth factor-beta production by synovial tissues from rheumatoid patients and streptococcal cell wall arthritic rats. Studies on secretion by synovial fibroblast-like cells and immunohistologic localization. J Immunol. 1989 Aug 15;143(4):1142–1148. [PubMed] [Google Scholar]
  25. Laiho M., Saksela O., Andreasen P. A., Keski-Oja J. Enhanced production and extracellular deposition of the endothelial-type plasminogen activator inhibitor in cultured human lung fibroblasts by transforming growth factor-beta. J Cell Biol. 1986 Dec;103(6 Pt 1):2403–2410. doi: 10.1083/jcb.103.6.2403. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Matrisian L. M., Leroy P., Ruhlmann C., Gesnel M. C., Breathnach R. Isolation of the oncogene and epidermal growth factor-induced transin gene: complex control in rat fibroblasts. Mol Cell Biol. 1986 May;6(5):1679–1686. doi: 10.1128/mcb.6.5.1679. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Mauviel A., Teyton L., Bhatnagar R., Penfornis H., Laurent M., Hartmann D., Bonaventure J., Loyau G., Saklatvala J., Pujol J. P. Interleukin-1 alpha modulates collagen gene expression in cultured synovial cells. Biochem J. 1988 May 15;252(1):247–255. doi: 10.1042/bj2520247. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Mizel S. B., Dayer J. M., Krane S. M., Mergenhagen S. E. Stimulation of rheumatoid synovial cell collagenase and prostaglandin production by partially purified lymphocyte-activating factor (interleukin 1). Proc Natl Acad Sci U S A. 1981 Apr;78(4):2474–2477. doi: 10.1073/pnas.78.4.2474. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Mochan E., Uhl J., Newton R. Interleukin 1 stimulation of synovial cell plasminogen activator production. J Rheumatol. 1986 Feb;13(1):15–19. [PubMed] [Google Scholar]
  30. Murphy G., Hembry R. M., Reynolds J. J. Characterization of a specific antiserum to rabbit stromelysin and demonstration of the synthesis of collagenase and stromelysin by stimulated rabbit articular chondrocytes. Coll Relat Res. 1986 Oct;6(4):351–363. doi: 10.1016/s0174-173x(86)80005-x. [DOI] [PubMed] [Google Scholar]
  31. Noda M., Rodan G. A. Type beta transforming growth factor (TGF beta) regulation of alkaline phosphatase expression and other phenotype-related mRNAs in osteoblastic rat osteosarcoma cells. J Cell Physiol. 1987 Dec;133(3):426–437. doi: 10.1002/jcp.1041330303. [DOI] [PubMed] [Google Scholar]
  32. Noda M., Yoon K., Prince C. W., Butler W. T., Rodan G. A. Transcriptional regulation of osteopontin production in rat osteosarcoma cells by type beta transforming growth factor. J Biol Chem. 1988 Sep 25;263(27):13916–13921. [PubMed] [Google Scholar]
  33. Nugent M. A., Newman M. J. Inhibition of normal rat kidney cell growth by transforming growth factor-beta is mediated by collagen. J Biol Chem. 1989 Oct 25;264(30):18060–18067. [PubMed] [Google Scholar]
  34. Penttinen R. P., Kobayashi S., Bornstein P. Transforming growth factor beta increases mRNA for matrix proteins both in the presence and in the absence of changes in mRNA stability. Proc Natl Acad Sci U S A. 1988 Feb;85(4):1105–1108. doi: 10.1073/pnas.85.4.1105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Postlethwaite A. E., Raghow R., Stricklin G. P., Poppleton H., Seyer J. M., Kang A. H. Modulation of fibroblast functions by interleukin 1: increased steady-state accumulation of type I procollagen messenger RNAs and stimulation of other functions but not chemotaxis by human recombinant interleukin 1 alpha and beta. J Cell Biol. 1988 Feb;106(2):311–318. doi: 10.1083/jcb.106.2.311. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Pulleyblank D. E., Booth G. M. Improved methods for the fluorographic detection of weak beta-emitting radioisotopes in Agarose and acrylamide gel electrophoresis media. J Biochem Biophys Methods. 1981 Jun;4(5-6):339–346. doi: 10.1016/0165-022x(81)90074-9. [DOI] [PubMed] [Google Scholar]
  37. Roberts A. B., Sporn M. B., Assoian R. K., Smith J. M., Roche N. S., Wakefield L. M., Heine U. I., Liotta L. A., Falanga V., Kehrl J. H. Transforming growth factor type beta: rapid induction of fibrosis and angiogenesis in vivo and stimulation of collagen formation in vitro. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4167–4171. doi: 10.1073/pnas.83.12.4167. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Rossi P., Karsenty G., Roberts A. B., Roche N. S., Sporn M. B., de Crombrugghe B. A nuclear factor 1 binding site mediates the transcriptional activation of a type I collagen promoter by transforming growth factor-beta. Cell. 1988 Feb 12;52(3):405–414. doi: 10.1016/s0092-8674(88)80033-3. [DOI] [PubMed] [Google Scholar]
  39. Sporn M. B., Roberts A. B., Wakefield L. M., de Crombrugghe B. Some recent advances in the chemistry and biology of transforming growth factor-beta. J Cell Biol. 1987 Sep;105(3):1039–1045. doi: 10.1083/jcb.105.3.1039. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Sykes B., Puddle B., Francis M., Smith R. The estimation of two collagens from human dermis by interrupted gel electrophoresis. Biochem Biophys Res Commun. 1976 Oct 18;72(4):1472–1480. doi: 10.1016/s0006-291x(76)80180-5. [DOI] [PubMed] [Google Scholar]
  41. Vuorio T., Mäkelä J. K., Kähäri V. M., Vuorio E. Coordinated regulation of type I and type III collagen production and mRNA levels of pro alpha 1(I) and pro alpha 2(I) collagen in cultured morphea fibroblasts. Arch Dermatol Res. 1987;279(3):154–160. doi: 10.1007/BF00413250. [DOI] [PubMed] [Google Scholar]
  42. Wahl S. M., Hunt D. A., Wakefield L. M., McCartney-Francis N., Wahl L. M., Roberts A. B., Sporn M. B. Transforming growth factor type beta induces monocyte chemotaxis and growth factor production. Proc Natl Acad Sci U S A. 1987 Aug;84(16):5788–5792. doi: 10.1073/pnas.84.16.5788. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Yaron I., Meyer F. A., Dayer J. M., Yaron M. Human recombinant interleukin-1 beta stimulates glycosaminoglycan production in human synovial fibroblast cultures. Arthritis Rheum. 1987 Apr;30(4):424–430. doi: 10.1002/art.1780300410. [DOI] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES