Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1992 Jun 1;89(11):5068–5072. doi: 10.1073/pnas.89.11.5068

Interleukin 6: insights to its function in skin by overexpression in transgenic mice.

K Turksen 1, T Kupper 1, L Degenstein 1, I Williams 1, E Fuchs 1
PMCID: PMC49230  PMID: 1375756

Abstract

Interleukin 6 (IL-6) is a cytokine that mediates a wide range of inflammatory and immune responses. Its expression is elevated in inflammatory or immunodeficient diseases, including psoriasis, rheumatoid arthritis, and AIDS. To explore the role of IL-6 in skin, we utilized a human keratin 14 (K14) promoter to express IL-6 in the basal cells of stratified squamous epithelia of transgenic mice. Mice expressing the K14-IL-6 transgene were smaller than normal and exhibited retarded hair growth. Surprisingly, IL-6 expression did not lead to enhanced epidermal proliferation, but it did result in a thicker stratum corneum, with an otherwise seemingly normal program of differentiation. IL-6 expression did not lead to leukocytic infiltration, making it unlikely that it has direct proinflammatory activity in skin. Based on this study, one role of IL-6 relevant to host defense may be to enhance the stratum corneum, thereby providing increased protection from injurious stimuli or infection. If IL-6 plays additional roles in the skin, it is likely to act synergistically with factors that IL-6 alone cannot induce.

Full text

PDF
5068

Images in this article

5069Image
on p.5069
5069Image
on p.5069
5070Image
on p.5070
5070Image
on p.5070
5071Image
on p.5071

Selected References

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

  1. Barrandon Y., Green H. Cell migration is essential for sustained growth of keratinocyte colonies: the roles of transforming growth factor-alpha and epidermal growth factor. Cell. 1987 Sep 25;50(7):1131–1137. doi: 10.1016/0092-8674(87)90179-6. [DOI] [PubMed] [Google Scholar]
  2. Bernard B. A., Asselineau D., Schaffar-Deshayes L., Darmon M. Y. Abnormal sequence of expression of differentiation markers in psoriatic epidermis: inversion of two steps in the differentiation program? J Invest Dermatol. 1988 Jun;90(6):801–805. doi: 10.1111/1523-1747.ep12462014. [DOI] [PubMed] [Google Scholar]
  3. Brandt S. J., Bodine D. M., Dunbar C. E., Nienhuis A. W. Dysregulated interleukin 6 expression produces a syndrome resembling Castleman's disease in mice. J Clin Invest. 1990 Aug;86(2):592–599. doi: 10.1172/JCI114749. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chiu C. P., Moulds C., Coffman R. L., Rennick D., Lee F. Multiple biological activities are expressed by a mouse interleukin 6 cDNA clone isolated from bone marrow stromal cells. Proc Natl Acad Sci U S A. 1988 Oct;85(19):7099–7103. doi: 10.1073/pnas.85.19.7099. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Coulombe P. A., Kopan R., Fuchs E. Expression of keratin K14 in the epidermis and hair follicle: insights into complex programs of differentiation. J Cell Biol. 1989 Nov;109(5):2295–2312. doi: 10.1083/jcb.109.5.2295. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Fong Y., Moldawer L. L., Marano M., Wei H., Tatter S. B., Clarick R. H., Santhanam U., Sherris D., May L. T., Sehgal P. B. Endotoxemia elicits increased circulating beta 2-IFN/IL-6 in man. J Immunol. 1989 Apr 1;142(7):2321–2324. [PubMed] [Google Scholar]
  7. Grossman R. M., Krueger J., Yourish D., Granelli-Piperno A., Murphy D. P., May L. T., Kupper T. S., Sehgal P. B., Gottlieb A. B. Interleukin 6 is expressed in high levels in psoriatic skin and stimulates proliferation of cultured human keratinocytes. Proc Natl Acad Sci U S A. 1989 Aug;86(16):6367–6371. doi: 10.1073/pnas.86.16.6367. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Helfgott D. C., Tatter S. B., Santhanam U., Clarick R. H., Bhardwaj N., May L. T., Sehgal P. B. Multiple forms of IFN-beta 2/IL-6 in serum and body fluids during acute bacterial infection. J Immunol. 1989 Feb 1;142(3):948–953. [PubMed] [Google Scholar]
  9. Hoffman-Liebermann B., Liebermann D. A. Interleukin-6- and leukemia inhibitory factor-induced terminal differentiation of myeloid leukemia cells is blocked at an intermediate stage by constitutive c-myc. Mol Cell Biol. 1991 May;11(5):2375–2381. doi: 10.1128/mcb.11.5.2375. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kirnbauer R., Köck A., Schwarz T., Urbanski A., Krutmann J., Borth W., Damm D., Shipley G., Ansel J. C., Luger T. A. IFN-beta 2, B cell differentiation factor 2, or hybridoma growth factor (IL-6) is expressed and released by human epidermal cells and epidermoid carcinoma cell lines. J Immunol. 1989 Mar 15;142(6):1922–1928. [PubMed] [Google Scholar]
  11. Krueger J. G., Krane J. F., Carter D. M., Gottlieb A. B. Role of growth factors, cytokines, and their receptors in the pathogenesis of psoriasis. J Invest Dermatol. 1990 Jun;94(6 Suppl):135S–140S. doi: 10.1111/1523-1747.ep12876121. [DOI] [PubMed] [Google Scholar]
  12. Kupper T. S. Immune and inflammatory processes in cutaneous tissues. Mechanisms and speculations. J Clin Invest. 1990 Dec;86(6):1783–1789. doi: 10.1172/JCI114907. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Moll R., Franke W. W., Schiller D. L., Geiger B., Krepler R. The catalog of human cytokeratins: patterns of expression in normal epithelia, tumors and cultured cells. Cell. 1982 Nov;31(1):11–24. doi: 10.1016/0092-8674(82)90400-7. [DOI] [PubMed] [Google Scholar]
  14. Moses H. L., Yang E. Y., Pietenpol J. A. TGF-beta stimulation and inhibition of cell proliferation: new mechanistic insights. Cell. 1990 Oct 19;63(2):245–247. doi: 10.1016/0092-8674(90)90155-8. [DOI] [PubMed] [Google Scholar]
  15. Neuner P., Urbanski A., Trautinger F., Möller A., Kirnbauer R., Kapp A., Schöpf E., Schwarz T., Luger T. A. Increased IL-6 production by monocytes and keratinocytes in patients with psoriasis. J Invest Dermatol. 1991 Jul;97(1):27–33. doi: 10.1111/1523-1747.ep12477880. [DOI] [PubMed] [Google Scholar]
  16. Nijsten M. W., de Groot E. R., ten Duis H. J., Klasen H. J., Hack C. E., Aarden L. A. Serum levels of interleukin-6 and acute phase responses. Lancet. 1987 Oct 17;2(8564):921–921. doi: 10.1016/s0140-6736(87)91413-9. [DOI] [PubMed] [Google Scholar]
  17. Sehgal P. B. Interleukin-6: molecular pathophysiology. J Invest Dermatol. 1990 Jun;94(6 Suppl):2S–6S. doi: 10.1111/1523-1747.ep12874963. [DOI] [PubMed] [Google Scholar]
  18. Sticherling M., Bornscheuer E., Schröder J. M., Christophers E. Localization of neutrophil-activating peptide-1/interleukin-8-immunoreactivity in normal and psoriatic skin. J Invest Dermatol. 1991 Jan;96(1):26–30. doi: 10.1111/1523-1747.ep12514689. [DOI] [PubMed] [Google Scholar]
  19. Stoler A., Kopan R., Duvic M., Fuchs E. Use of monospecific antisera and cRNA probes to localize the major changes in keratin expression during normal and abnormal epidermal differentiation. J Cell Biol. 1988 Aug;107(2):427–446. doi: 10.1083/jcb.107.2.427. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Suematsu S., Matsuda T., Aozasa K., Akira S., Nakano N., Ohno S., Miyazaki J., Yamamura K., Hirano T., Kishimoto T. IgG1 plasmacytosis in interleukin 6 transgenic mice. Proc Natl Acad Sci U S A. 1989 Oct;86(19):7547–7551. doi: 10.1073/pnas.86.19.7547. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Taga T., Hibi M., Hirata Y., Yamasaki K., Yasukawa K., Matsuda T., Hirano T., Kishimoto T. Interleukin-6 triggers the association of its receptor with a possible signal transducer, gp130. Cell. 1989 Aug 11;58(3):573–581. doi: 10.1016/0092-8674(89)90438-8. [DOI] [PubMed] [Google Scholar]
  22. Tepper R. I., Levinson D. A., Stanger B. Z., Campos-Torres J., Abbas A. K., Leder P. IL-4 induces allergic-like inflammatory disease and alters T cell development in transgenic mice. Cell. 1990 Aug 10;62(3):457–467. doi: 10.1016/0092-8674(90)90011-3. [DOI] [PubMed] [Google Scholar]
  23. Van Snick J. Interleukin-6: an overview. Annu Rev Immunol. 1990;8:253–278. doi: 10.1146/annurev.iy.08.040190.001345. [DOI] [PubMed] [Google Scholar]
  24. Vassar R., Fuchs E. Transgenic mice provide new insights into the role of TGF-alpha during epidermal development and differentiation. Genes Dev. 1991 May;5(5):714–727. doi: 10.1101/gad.5.5.714. [DOI] [PubMed] [Google Scholar]
  25. Vassar R., Rosenberg M., Ross S., Tyner A., Fuchs E. Tissue-specific and differentiation-specific expression of a human K14 keratin gene in transgenic mice. Proc Natl Acad Sci U S A. 1989 Mar;86(5):1563–1567. doi: 10.1073/pnas.86.5.1563. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Weiss R. A., Eichner R., Sun T. T. Monoclonal antibody analysis of keratin expression in epidermal diseases: a 48- and 56-kdalton keratin as molecular markers for hyperproliferative keratinocytes. J Cell Biol. 1984 Apr;98(4):1397–1406. doi: 10.1083/jcb.98.4.1397. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES