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. 1986 Oct 1;103(4):1349–1354. doi: 10.1083/jcb.103.4.1349

Normal human epidermis contains an interferon-like protein

PMCID: PMC2114318  PMID: 3771639

Abstract

Interferons have been postulated to participate in growth regulation of normal body tissues and are known to inhibit growth of human epidermal keratinocytes in vitro. Polyclonal antibodies to recombinant human interferon-alpha, purified by passage over an affinity column (Sepharose coupled to the recombinant interferon), used in the indirect immunofluorescent method specifically stained the proliferative (basal) compartment of human epidermis in histological cross-sections of normal skin and in cultured keratinocyte colonies. Extracts prepared from healthy nonvirally infected keratinocyte cultures contained interferon activity as determined by viral plaque inhibition assay. Using the Western blotting technique column-purified antibodies and antisera to recombinant human interferon-alpha recognized a band of approximately 40 kD when reacted with both extracted keratinocyte proteins and recombinant human interferon-alpha standards, that gave in addition a band of approximately 20 kD. The above findings suggest that interferon or a closely related protein is present in the proliferative compartment of normal epidermis in the absence of viral infection and therefore may serve as a physiological modulator of epidermal growth.

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Selected References

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  1. BULLOUGH W. S. The control of mitotic activity in adult mammalian tissues. Biol Rev Camb Philos Soc. 1962 Aug;37:307–342. doi: 10.1111/j.1469-185x.1962.tb01615.x. [DOI] [PubMed] [Google Scholar]
  2. Borden E. C. Progress toward therapeutic application of interferons, 1979-1983. Cancer. 1984 Dec 1;54(11 Suppl):2770–2776. doi: 10.1002/1097-0142(19841201)54:2+<2770::aid-cncr2820541425>3.0.co;2-0. [DOI] [PubMed] [Google Scholar]
  3. Boyce S. T., Ham R. G. Calcium-regulated differentiation of normal human epidermal keratinocytes in chemically defined clonal culture and serum-free serial culture. J Invest Dermatol. 1983 Jul;81(1 Suppl):33s–40s. doi: 10.1111/1523-1747.ep12540422. [DOI] [PubMed] [Google Scholar]
  4. Chopra D. P., Flaxman B. A. The effect of vitamin A on growth and differentiation of human keratinocytes in vitro. J Invest Dermatol. 1975 Jan;64(1):19–22. doi: 10.1111/1523-1747.ep12540883. [DOI] [PubMed] [Google Scholar]
  5. Dalton B. J., Paucker K. Antigenic properties of human lymphoblastoid interferons. Infect Immun. 1979 Feb;23(2):244–248. doi: 10.1128/iai.23.2.244-248.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Foidart J. M., Bere E. W., Jr, Yaar M., Rennard S. I., Gullino M., Martin G. R., Katz S. I. Distribution and immunoelectron microscopic localization of laminin, a noncollagenous basement membrane glycoprotein. Lab Invest. 1980 Mar;42(3):336–342. [PubMed] [Google Scholar]
  7. Gilchrest B. A., Marshall W. L., Karassik R. L., Weinstein R., Maciag T. Characterization and partial purification of keratinocyte growth factor from the hypothalamus. J Cell Physiol. 1984 Sep;120(3):377–383. doi: 10.1002/jcp.1041200316. [DOI] [PubMed] [Google Scholar]
  8. Gilchrest B. A., Nemore R. E., Maciag T. Growth of human keratinocytes on fibronectin -coated plates. Cell Biol Int Rep. 1980 Nov;4(11):1009–1016. doi: 10.1016/0309-1651(80)90173-3. [DOI] [PubMed] [Google Scholar]
  9. Gilchrest B. A. Prior chronic sun exposure decreases the lifespan of human skin fibroblasts in vitro. J Gerontol. 1980 Jul;35(4):537–541. doi: 10.1093/geronj/35.4.537. [DOI] [PubMed] [Google Scholar]
  10. Gilchrest B. A. Relationship between actinic damage and chronologic aging in keratinocyte cultures of human skin. J Invest Dermatol. 1979 May;72(5):219–223. doi: 10.1111/1523-1747.ep12530769. [DOI] [PubMed] [Google Scholar]
  11. Green H. Cyclic AMP in relation to proliferation of the epidermal cell: a new view. Cell. 1978 Nov;15(3):801–811. doi: 10.1016/0092-8674(78)90265-9. [DOI] [PubMed] [Google Scholar]
  12. Green H., Kehinde O., Thomas J. Growth of cultured human epidermal cells into multiple epithelia suitable for grafting. Proc Natl Acad Sci U S A. 1979 Nov;76(11):5665–5668. doi: 10.1073/pnas.76.11.5665. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gresser I., Thomas M. T., Brouty-Boyé D. Effect of interferon treatment of L1210 cells in vitro on tumour and colony formation. Nat New Biol. 1971 May 5;231(18):20–21. [PubMed] [Google Scholar]
  14. Grove G. L., Anderton R. L., Smith J. G., Jr Cytophotometric studies of epidermal proliferation in psoriatic and normal skin. J Invest Dermatol. 1976 Apr;66(4):236–238. doi: 10.1111/1523-1747.ep12482151. [DOI] [PubMed] [Google Scholar]
  15. Hicks N. J., Morris A. G., Burke D. C. Partial reversion of the transformed phenotype of murine sarcoma virus-transformed cells in the presence of interferon: a possible mechanism for the anti-tumour effect of interferon. J Cell Sci. 1981 Jun;49:225–236. doi: 10.1242/jcs.49.1.225. [DOI] [PubMed] [Google Scholar]
  16. Inglot A. D. Interferons and growth factors viewed as two families of hormones with opposing actions. Tex Rep Biol Med. 1981;41:402–410. [PubMed] [Google Scholar]
  17. Lebon P., Girard S., Thépot F., Chany C. The presence of alpha-interferon in human amniotic fluid. J Gen Virol. 1982 Apr;59(Pt 2):393–396. doi: 10.1099/0022-1317-59-2-393. [DOI] [PubMed] [Google Scholar]
  18. Lehmann W., Graetz H., Schunck H., Schütt M., Langen P. Aspects of chalone action. Acta Histochem Suppl. 1983;27:63–71. [PubMed] [Google Scholar]
  19. Maciag T., Nemore R. E., Weinstein R., Gilchrest B. A. An endocrine approach to the control of epidermal growth: serum-free cultivation of human keratinocytes. Science. 1981 Mar 27;211(4489):1452–1454. doi: 10.1126/science.6970413. [DOI] [PubMed] [Google Scholar]
  20. Marks F., Richter K. H. A request for a more serious approach to the chalone concept. Br J Dermatol. 1984 Jul;111 (Suppl 27):58–63. doi: 10.1111/j.1365-2133.1984.tb15582.x. [DOI] [PubMed] [Google Scholar]
  21. Moore R. N., Larsen H. S., Horohov D. W., Rouse B. T. Endogenous regulation of macrophage proliferative expansion by colony-stimulating factor-induced interferon. Science. 1984 Jan 13;223(4632):178–181. doi: 10.1126/science.6606850. [DOI] [PubMed] [Google Scholar]
  22. Nickoloff B. J., Basham T. Y., Merigan T. C., Morhenn V. B. Antiproliferative effects of recombinant alpha- and gamma-interferons on cultured human keratinocytes. Lab Invest. 1984 Dec;51(6):697–701. [PubMed] [Google Scholar]
  23. O'Keefe E. J., Payne R. E., Russell N. Keratinocyte growth-promoting activity from human placenta. J Cell Physiol. 1985 Sep;124(3):439–445. doi: 10.1002/jcp.1041240312. [DOI] [PubMed] [Google Scholar]
  24. Peehl D. M., Ham R. G. Growth and differentiation of human keratinocytes without a feeder layer or conditioned medium. In Vitro. 1980 Jun;16(6):516–525. doi: 10.1007/BF02626465. [DOI] [PubMed] [Google Scholar]
  25. Pestka S., Kelder B., Tarnowski D. K., Tarnowski S. J. Specific immunoassay for protein dimers, trimers, and higher oligomers. Anal Biochem. 1983 Jul 15;132(2):328–333. doi: 10.1016/0003-2697(83)90015-5. [DOI] [PubMed] [Google Scholar]
  26. Pickering L. A., Kronenberg L. H., Stewart W. E., 2nd Spontaneous production of human interferon. Proc Natl Acad Sci U S A. 1980 Oct;77(10):5938–5942. doi: 10.1073/pnas.77.10.5938. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Rheinwald J. G., Green H. Epidermal growth factor and the multiplication of cultured human epidermal keratinocytes. Nature. 1977 Feb 3;265(5593):421–424. doi: 10.1038/265421a0. [DOI] [PubMed] [Google Scholar]
  28. Rubinstein S., Familletti P. C., Pestka S. Convenient assay for interferons. J Virol. 1981 Feb;37(2):755–758. doi: 10.1128/jvi.37.2.755-758.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Schnipper L. E., Levin M., Crumpacker C. S., Gilchrest B. A. Virus replication and induction of interferon in human epidermal keratinocytes following infection with herpes simplex virus. J Invest Dermatol. 1984 Jan;82(1):94–96. doi: 10.1111/1523-1747.ep12259193. [DOI] [PubMed] [Google Scholar]
  30. Simon M., Green H. Participation of membrane-associated proteins in the formation of the cross-linked envelope of the keratinocyte. Cell. 1984 Apr;36(4):827–834. doi: 10.1016/0092-8674(84)90032-1. [DOI] [PubMed] [Google Scholar]
  31. Sporn M. B., Dunlop N. M., Yuspa S. H. Retinyl acetate: effect on cellular content of RNA in epidermis in cell culture in chemically defined medium. Science. 1973 Nov 16;182(4113):722–723. doi: 10.1126/science.182.4113.722. [DOI] [PubMed] [Google Scholar]
  32. Staehelin T., Durrer B., Schmidt J., Takacs B., Stocker J., Miggiano V., Stähli C., Rubinstein M., Levy W. P., Hershberg R. Production of hybridomas secreting monoclonal antibodies to the human leukocyte interferons. Proc Natl Acad Sci U S A. 1981 Mar;78(3):1848–1852. doi: 10.1073/pnas.78.3.1848. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Staehelin T., Hobbs D. S., Kung H., Lai C. Y., Pestka S. Purification and characterization of recombinant human leukocyte interferon (IFLrA) with monoclonal antibodies. J Biol Chem. 1981 Sep 25;256(18):9750–9754. [PubMed] [Google Scholar]
  34. Stanley J. R., Hawley-Nelson P., Yaar M., Martin G. R., Katz S. I. Laminin and bullous pemphigoid antigen are distinct basement membrane proteins synthesized by epidermal cells. J Invest Dermatol. 1982 Jun;78(6):456–459. doi: 10.1111/1523-1747.ep12510132. [DOI] [PubMed] [Google Scholar]
  35. Stanley J. R., Woodley D. T., Katz S. I. Identification and partial characterization of pemphigoid antigen extracted from normal human skin. J Invest Dermatol. 1984 Jan;82(1):108–111. doi: 10.1111/1523-1747.ep12259224. [DOI] [PubMed] [Google Scholar]
  36. Stewart W. E., 2nd, Havell E. A. Characterization of a subspecies of mouse interferon cross-reactive on human cells and antigenically related to human leukocyte interferon. Virology. 1980 Feb;101(1):315–318. doi: 10.1016/0042-6822(80)90512-7. [DOI] [PubMed] [Google Scholar]
  37. Taylor-Papadimitriou J., Shearer M., Rozengurt E. Inhibitory effect of interferon on cellular DNA synthesis: modulation by pure mitogenic factors. J Interferon Res. 1981;1(3):401–409. doi: 10.1089/jir.1981.1.401. [DOI] [PubMed] [Google Scholar]
  38. Thomas D. R., Philpott G. W., Jaffe B. M. The relationship between concentration of prostaglandin E and rates of cell replication. Exp Cell Res. 1974 Mar 15;84(1):40–46. doi: 10.1016/0014-4827(74)90377-2. [DOI] [PubMed] [Google Scholar]
  39. Towbin H., Staehelin T., Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350–4354. doi: 10.1073/pnas.76.9.4350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Yaar M., Karassik R. L., Schnipper L. E., Gilchrest B. A. Effects of alpha and beta interferons on cultured human keratinocytes. J Invest Dermatol. 1985 Jul;85(1):70–74. doi: 10.1111/1523-1747.ep12275353. [DOI] [PubMed] [Google Scholar]

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