Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1990 Feb;85(2):605–608. doi: 10.1172/JCI114481

Marked synergism between tumor necrosis factor-alpha and interferon-gamma in regulation of keratinocyte-derived adhesion molecules and chemotactic factors.

J N Barker 1, V Sarma 1, R S Mitra 1, V M Dixit 1, B J Nickoloff 1
PMCID: PMC296467  PMID: 2105343

Abstract

T lymphocytes and mononuclear cells preferentially accumulate in the epidermis in inflammatory skin disease. To determine the role of keratinocytes in both the chemotaxis and adhesion of these cells to the epidermis, cultured keratinocytes were incubated with IFN-gamma and tumor necrosis factor-alpha (TNF-alpha), and mRNA detected and quantitated for IL-8, monocyte chemotaxis and activating factor, and intercellular adhesion molecule-1. Whereas induction of these mRNAs was either absent, or relatively weak and transient, to either IFN-gamma or TNF-alpha alone, when administered in combination there was a dramatic increase and persistence in the induction of all three genes. Pretreatment of the keratinocytes with cycloheximide failed to eliminate transcription, implying that all three are primary response genes. Transforming growth factor-beta, which modulates other keratinocyte functions (not related to adhesion or chemotaxis of inflammatory cells) failed to induce any of the genes. These novel findings potentially explain the selective recruitment of T cells and monocytes observed in inflammatory skin disease, because IFN-gamma and TNF-alpha can co-ordinately regulate keratinocyte-derived chemoattractants and adhesion molecule production.

Full text

PDF
605

Images in this article

606Image
on p.606

Selected References

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

  1. Butcher E. C. The regulation of lymphocyte traffic. Curr Top Microbiol Immunol. 1986;128:85–122. doi: 10.1007/978-3-642-71272-2_3. [DOI] [PubMed] [Google Scholar]
  2. Cotran R. S., Gimbrone M. A., Jr, Bevilacqua M. P., Mendrick D. L., Pober J. S. Induction and detection of a human endothelial activation antigen in vivo. J Exp Med. 1986 Aug 1;164(2):661–666. doi: 10.1084/jem.164.2.661. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Dustin M. L., Singer K. H., Tuck D. T., Springer T. A. Adhesion of T lymphoblasts to epidermal keratinocytes is regulated by interferon gamma and is mediated by intercellular adhesion molecule 1 (ICAM-1). J Exp Med. 1988 Apr 1;167(4):1323–1340. doi: 10.1084/jem.167.4.1323. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  5. Freemont A. J., Ford W. L. Functional and morphological changes in post-capillary venules in relation to lymphocytic infiltration into BCG-induced granulomata in rat skin. J Pathol. 1985 Sep;147(1):1–12. doi: 10.1002/path.1711470102. [DOI] [PubMed] [Google Scholar]
  6. Griffiths C. E., Esmann J., Fisher G. J., Voorhees J. J., Nickoloff B. J. Differential modulation of keratinocyte intercellular adhesion molecule-I expression by gamma interferon and phorbol ester: evidence for involvement of protein kinase C signal transduction. Br J Dermatol. 1990 Mar;122(3):333–342. doi: 10.1111/j.1365-2133.1990.tb08281.x. [DOI] [PubMed] [Google Scholar]
  7. Griffiths C. E., Nickoloff B. J. Keratinocyte intercellular adhesion molecule-1 (ICAM-1) expression precedes dermal T lymphocytic infiltration in allergic contact dermatitis (Rhus dermatitis). Am J Pathol. 1989 Dec;135(6):1045–1053. [PMC free article] [PubMed] [Google Scholar]
  8. Griffiths C. E., Voorhees J. J., Nickoloff B. J. Gamma interferon induces different keratinocyte cellular patterns of expression of HLA-DR and DQ and intercellular adhesion molecule-I (ICAM-I) antigens. Br J Dermatol. 1989 Jan;120(1):1–8. doi: 10.1111/j.1365-2133.1989.tb07759.x. [DOI] [PubMed] [Google Scholar]
  9. Kupper T. S. Interleukin 1 and other human keratinocyte cytokines: molecular and functional characterization. Adv Dermatol. 1988;3:293–307. [PubMed] [Google Scholar]
  10. Larsen C. G., Anderson A. O., Appella E., Oppenheim J. J., Matsushima K. The neutrophil-activating protein (NAP-1) is also chemotactic for T lymphocytes. Science. 1989 Mar 17;243(4897):1464–1466. doi: 10.1126/science.2648569. [DOI] [PubMed] [Google Scholar]
  11. Matsushima K., Larsen C. G., DuBois G. C., Oppenheim J. J. Purification and characterization of a novel monocyte chemotactic and activating factor produced by a human myelomonocytic cell line. J Exp Med. 1989 Apr 1;169(4):1485–1490. doi: 10.1084/jem.169.4.1485. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Mommaas-Kienhuis A. M., Grayson S., Wijsman M. C., Vermeer B. J., Elias P. M. Low density lipoprotein receptor expression on keratinocytes in normal and psoriatic epidermis. J Invest Dermatol. 1987 Nov;89(5):513–517. doi: 10.1111/1523-1747.ep12461024. [DOI] [PubMed] [Google Scholar]
  13. Nickoloff B. J., Mitra R. S., Elder J. T., Fisher G. J., Voorhees J. J. Decreased growth inhibition by recombinant gamma interferon is associated with increased transforming growth factor-alpha production in keratinocytes cultured from psoriatic lesions. Br J Dermatol. 1989 Aug;121(2):161–174. doi: 10.1111/j.1365-2133.1989.tb01795.x. [DOI] [PubMed] [Google Scholar]
  14. Nickoloff B. J., Mitra R. S., Riser B. L., Dixit V. M., Varani J. Modulation of keratinocyte motility. Correlation with production of extracellular matrix molecules in response to growth promoting and antiproliferative factors. Am J Pathol. 1988 Sep;132(3):543–551. [PMC free article] [PubMed] [Google Scholar]
  15. Nickoloff B. J. Role of interferon-gamma in cutaneous trafficking of lymphocytes with emphasis on molecular and cellular adhesion events. Arch Dermatol. 1988 Dec;124(12):1835–1843. [PubMed] [Google Scholar]
  16. Pillai S., Bikle D. D., Eessalu T. E., Aggarwal B. B., Elias P. M. Binding and biological effects of tumor necrosis factor alpha on cultured human neonatal foreskin keratinocytes. J Clin Invest. 1989 Mar;83(3):816–821. doi: 10.1172/JCI113963. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Ternowitz T., Thestrup-Pedersen K. Epidermis and lymphocyte interactions during a tuberculin skin reaction. II. Epidermis contains specific lymphocyte chemotactic factors. J Invest Dermatol. 1986 Nov;87(5):613–616. doi: 10.1111/1523-1747.ep12455858. [DOI] [PubMed] [Google Scholar]
  18. Yoshimura T., Yuhki N., Moore S. K., Appella E., Lerman M. I., Leonard E. J. Human monocyte chemoattractant protein-1 (MCP-1). Full-length cDNA cloning, expression in mitogen-stimulated blood mononuclear leukocytes, and sequence similarity to mouse competence gene JE. FEBS Lett. 1989 Feb 27;244(2):487–493. doi: 10.1016/0014-5793(89)80590-3. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES