Skip to main content
Biochemical Journal logoLink to Biochemical Journal
. 1994 Sep 1;302(Pt 2):331–333. doi: 10.1042/bj3020331

Interleukin 10 up-regulates elastin gene expression in vivo and in vitro at the transcriptional level.

S Reitamo 1, A Remitz 1, K Tamai 1, I Ledo 1, J Uitto 1
PMCID: PMC1137232  PMID: 8092983

Abstract

In immune cells, such as T cells and monocytes, interleukin 10 (IL-10) has regulatory functions on a number of cytokines, including IL-1, IL-2, IL-8 and tumour necrosis factor-alpha expression. However, the effects of IL-10 have not previously been studied in detail in connective-tissue cells. In the present study, we show that recombinant human IL-10 at physiological concentrations has direct effects on the expression of the human elastin gene both in vivo and in vitro. Transgenic mice expressing a human elastin promoter/chloramphenicol acetyltransferase (CAT) reporter gene construct were injected subcutaneously with IL-10 (1-100 ng) and the site of injection was biopsied after 24 h. CAT assay revealed an increase of up to 3.5-fold in the promoter activity with 10 ng of IL-10. Transforming growth factor-beta 2 (TGF-beta 2) is known to up-regulate elastin gene expression in cultured fibroblasts. When IL-10 was added to such cultures, the effects of TGF-beta 2 on elastin mRNA levels were synergistically potentiated. These results suggest that IL-10 has an up-regulatory effect on elastin gene expression.

Full text

PDF
331

Images in this article

Selected References

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

  1. Bernstein E. F., Chen Y. Q., Tamai K., Shepley K. J., Resnik K. S., Zhang H., Tuan R., Mauviel A., Uitto J. Enhanced elastin and fibrillin gene expression in chronically photodamaged skin. J Invest Dermatol. 1994 Aug;103(2):182–186. doi: 10.1111/1523-1747.ep12392693. [DOI] [PubMed] [Google Scholar]
  2. Bogdan C., Paik J., Vodovotz Y., Nathan C. Contrasting mechanisms for suppression of macrophage cytokine release by transforming growth factor-beta and interleukin-10. J Biol Chem. 1992 Nov 15;267(32):23301–23308. [PubMed] [Google Scholar]
  3. Chomarat P., Rissoan M. C., Banchereau J., Miossec P. Interferon gamma inhibits interleukin 10 production by monocytes. J Exp Med. 1993 Feb 1;177(2):523–527. doi: 10.1084/jem.177.2.523. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Del Prete G., De Carli M., Almerigogna F., Giudizi M. G., Biagiotti R., Romagnani S. Human IL-10 is produced by both type 1 helper (Th1) and type 2 helper (Th2) T cell clones and inhibits their antigen-specific proliferation and cytokine production. J Immunol. 1993 Jan 15;150(2):353–360. [PubMed] [Google Scholar]
  5. Enk A. H., Katz S. I. Identification and induction of keratinocyte-derived IL-10. J Immunol. 1992 Jul 1;149(1):92–95. [PubMed] [Google Scholar]
  6. Fazio M. J., Olsen D. R., Kauh E. A., Baldwin C. T., Indik Z., Ornstein-Goldstein N., Yeh H., Rosenbloom J., Uitto J. Cloning of full-length elastin cDNAs from a human skin fibroblast recombinant cDNA library: further elucidation of alternative splicing utilizing exon-specific oligonucleotides. J Invest Dermatol. 1988 Nov;91(5):458–464. doi: 10.1111/1523-1747.ep12476591. [DOI] [PubMed] [Google Scholar]
  7. Fiorentino D. F., Bond M. W., Mosmann T. R. Two types of mouse T helper cell. IV. Th2 clones secrete a factor that inhibits cytokine production by Th1 clones. J Exp Med. 1989 Dec 1;170(6):2081–2095. doi: 10.1084/jem.170.6.2081. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fiorentino D. F., Zlotnik A., Vieira P., Mosmann T. R., Howard M., Moore K. W., O'Garra A. IL-10 acts on the antigen-presenting cell to inhibit cytokine production by Th1 cells. J Immunol. 1991 May 15;146(10):3444–3451. [PubMed] [Google Scholar]
  9. 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]
  10. Howard M., O'Garra A. Biological properties of interleukin 10. Immunol Today. 1992 Jun;13(6):198–200. doi: 10.1016/0167-5699(92)90153-X. [DOI] [PubMed] [Google Scholar]
  11. Hsu-Wong S., Katchman S. D., Ledo I., Wu M., Khillan J., Bashir M. M., Rosenbloom J., Uitto J. Tissue-specific and developmentally regulated expression of human elastin promoter activity in transgenic mice. J Biol Chem. 1994 Jul 8;269(27):18072–18075. [PubMed] [Google Scholar]
  12. Kähäri V. M., Fazio M. J., Chen Y. Q., Bashir M. M., Rosenbloom J., Uitto J. Deletion analyses of 5'-flanking region of the human elastin gene. Delineation of functional promoter and regulatory cis-elements. J Biol Chem. 1990 Jun 5;265(16):9485–9490. [PubMed] [Google Scholar]
  13. Kähäri V. M., Olsen D. R., Rhudy R. W., Carrillo P., Chen Y. Q., Uitto J. Transforming growth factor-beta up-regulates elastin gene expression in human skin fibroblasts. Evidence for post-transcriptional modulation. Lab Invest. 1992 May;66(5):580–588. [PubMed] [Google Scholar]
  14. Liu J. M., Davidson J. M. The elastogenic effect of recombinant transforming growth factor-beta on porcine aortic smooth muscle cells. Biochem Biophys Res Commun. 1988 Aug 15;154(3):895–901. doi: 10.1016/0006-291x(88)90224-0. [DOI] [PubMed] [Google Scholar]
  15. Mitchell R. E. Chronic solar dermatosis: a light and electron microscopic study of the dermis. J Invest Dermatol. 1967 Mar;48(3):203–220. doi: 10.1038/jid.1967.33. [DOI] [PubMed] [Google Scholar]
  16. Moore K. W., Vieira P., Fiorentino D. F., Trounstine M. L., Khan T. A., Mosmann T. R. Homology of cytokine synthesis inhibitory factor (IL-10) to the Epstein-Barr virus gene BCRFI. Science. 1990 Jun 8;248(4960):1230–1234. doi: 10.1126/science.2161559. [DOI] [PubMed] [Google Scholar]
  17. Rivas J. M., Ullrich S. E. Systemic suppression of delayed-type hypersensitivity by supernatants from UV-irradiated keratinocytes. An essential role for keratinocyte-derived IL-10. J Immunol. 1992 Dec 15;149(12):3865–3871. [PubMed] [Google Scholar]
  18. Rosenbloom J., Bashir M., Kahari V. M., Uitto J. Elastin genes and regulation of their expression. Crit Rev Eukaryot Gene Expr. 1991;1(3):145–156. [PubMed] [Google Scholar]
  19. Thomas P. S. Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5201–5205. doi: 10.1073/pnas.77.9.5201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Vieira P., de Waal-Malefyt R., Dang M. N., Johnson K. E., Kastelein R., Fiorentino D. F., deVries J. E., Roncarolo M. G., Mosmann T. R., Moore K. W. Isolation and expression of human cytokine synthesis inhibitory factor cDNA clones: homology to Epstein-Barr virus open reading frame BCRFI. Proc Natl Acad Sci U S A. 1991 Feb 15;88(4):1172–1176. doi: 10.1073/pnas.88.4.1172. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Yssel H., De Waal Malefyt R., Roncarolo M. G., Abrams J. S., Lahesmaa R., Spits H., de Vries J. E. IL-10 is produced by subsets of human CD4+ T cell clones and peripheral blood T cells. J Immunol. 1992 Oct 1;149(7):2378–2384. [PubMed] [Google Scholar]
  22. de Waal Malefyt R., Abrams J., Bennett B., Figdor C. G., de Vries J. E. Interleukin 10(IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes. J Exp Med. 1991 Nov 1;174(5):1209–1220. doi: 10.1084/jem.174.5.1209. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. de Waal Malefyt R., Haanen J., Spits H., Roncarolo M. G., te Velde A., Figdor C., Johnson K., Kastelein R., Yssel H., de Vries J. E. Interleukin 10 (IL-10) and viral IL-10 strongly reduce antigen-specific human T cell proliferation by diminishing the antigen-presenting capacity of monocytes via downregulation of class II major histocompatibility complex expression. J Exp Med. 1991 Oct 1;174(4):915–924. doi: 10.1084/jem.174.4.915. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES