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. 1995 Apr;63(4):1223–1228. doi: 10.1128/iai.63.4.1223-1228.1995

In vitro modulation of keratinocyte-derived interleukin-1 alpha (IL-1 alpha) and peripheral blood mononuclear cell-derived IL-1 beta release in response to cutaneous commensal microorganisms.

C E Walters 1, E Ingham 1, E A Eady 1, J H Cove 1, J N Kearney 1, W J Cunliffe 1
PMCID: PMC173138  PMID: 7890376

Abstract

The ability of a range of skin commensal microorganisms to modulate interleukin-1 (IL-1) release by cultured human keratinocytes and peripheral blood mononuclear cells (PBMCs) was investigated by a combination of enzyme-linked immunosorbent assays and bioassays. Three fractions (formaldehyde-treated whole cells, culture supernatants, and cellular fractions) were prepared from Propionibacterium acnes, Propionibacterium granulosum, Staphylococcus epidermidis, Staphylococcus capitis, Staphylococcus hominis, and Malassezia furfur serovar B. The levels of immunochemical IL-1 alpha released by cultured keratinocytes during coincubations with these microbial fractions ranged from 0 to 136 pg/ml and were maximal after 72 h. No microbial fraction consistently upregulated immunochemical IL-1 alpha release by freshly isolated keratinocytes from two donors and a transformed cell line, all of which produced the cytokine constitutively to various extents. Bioassays revealed that most of the IL-1 released was biologically inactive. In contrast, whole cells of formaldehyde-treated P. granulosum and S. epidermidis significantly stimulated release of IL-1 beta by PBMCs from three donors compared with the negative control (culture medium). Release was maximal at 24 h. Coincubation with intact cells of the yeast M. furfur significantly decreased levels of IL-1 beta below the values for the negative control by PBMCs from all three donors. There was good correlation between bioassay data and immunoassay data for IL-1 beta, and the depressive effect of M. furfur cells on cytokine production by all three cultures of PBMCs was mirrored in the levels of bioactive cytokine. This reduction in IL-1 beta release by PBMCs by M. furfur may provide an explanation why dermatoses thought to be caused by this yeast are essentially noninflammatory or only mildly inflammatory.

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Selected References

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  1. Agace W., Hedges S., Andersson U., Andersson J., Ceska M., Svanborg C. Selective cytokine production by epithelial cells following exposure to Escherichia coli. Infect Immun. 1993 Feb;61(2):602–609. doi: 10.1128/iai.61.2.602-609.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Barker J. N., MacDonald D. M. Cutaneous lymphocyte trafficking in the inflammatory dermatoses. Br J Dermatol. 1992 Mar;126(3):211–215. doi: 10.1111/j.1365-2133.1992.tb00647.x. [DOI] [PubMed] [Google Scholar]
  3. Barker J. N., Mitra R. S., Griffiths C. E., Dixit V. M., Nickoloff B. J. Keratinocytes as initiators of inflammation. Lancet. 1991 Jan 26;337(8735):211–214. doi: 10.1016/0140-6736(91)92168-2. [DOI] [PubMed] [Google Scholar]
  4. Blanton R. A., Kupper T. S., McDougall J. K., Dower S. Regulation of interleukin 1 and its receptor in human keratinocytes. Proc Natl Acad Sci U S A. 1989 Feb;86(4):1273–1277. doi: 10.1073/pnas.86.4.1273. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Camp R., Fincham N., Ross J., Bird C., Gearing A. Potent inflammatory properties in human skin of interleukin-1 alpha-like material isolated from normal skin. J Invest Dermatol. 1990 Jun;94(6):735–741. doi: 10.1111/1523-1747.ep12874591. [DOI] [PubMed] [Google Scholar]
  6. Chu E., Rosenwasser L. J., Dinarello C. A., Lareau M., Geha R. S. Role of interleukin 1 in antigen-specific T cell proliferation. J Immunol. 1984 Mar;132(3):1311–1316. [PubMed] [Google Scholar]
  7. Cooper K. D., Hammerberg C., Baadsgaard O., Elder J. T., Chan L. S., Taylor R. S., Voorhees J. J., Fisher G. Interleukin-1 in human skin: dysregulation in psoriasis. J Invest Dermatol. 1990 Nov;95(5 Suppl):24S–26S. doi: 10.1111/1523-1747.ep12505698. [DOI] [PubMed] [Google Scholar]
  8. Cove J. H., Holland K. T., Cunliffe W. J. The vitamin requirements of staphylococci isolated from human skin. J Appl Bacteriol. 1980 Aug;49(1):29–37. doi: 10.1111/j.1365-2672.1980.tb01041.x. [DOI] [PubMed] [Google Scholar]
  9. De Young L. M., Spires D. A., Ballaron S. J., Cummins C. S., Young J. M., Allison A. C. Acne-like chronic inflammatory activity of Propionibacterium acnes preparations in an animal model: correlation with ability to stimulate the reticuloendothelial system. J Invest Dermatol. 1985 Sep;85(3):255–258. doi: 10.1111/1523-1747.ep12276732. [DOI] [PubMed] [Google Scholar]
  10. Dinarello C. A. The biology of interleukin 1 and comparison to tumor necrosis factor. Immunol Lett. 1987 Dec;16(3-4):227–231. doi: 10.1016/0165-2478(87)90151-9. [DOI] [PubMed] [Google Scholar]
  11. Djeu J. Y., Blanchard D. K., Richards A. L., Friedman H. Tumor necrosis factor induction by Candida albicans from human natural killer cells and monocytes. J Immunol. 1988 Dec 1;141(11):4047–4052. [PubMed] [Google Scholar]
  12. Falk W., Krammer P. H., Männel D. N. A new assay for interleukin-1 in the presence of interleukin-2. J Immunol Methods. 1987 May 4;99(1):47–52. doi: 10.1016/0022-1759(87)90030-5. [DOI] [PubMed] [Google Scholar]
  13. Gruaz-Chatellard D., Baumberger C., Saurat J. H., Dayer J. M. Interleukin 1 receptor antagonist in human epidermis and cultured keratinocytes. FEBS Lett. 1991 Dec 2;294(1-2):137–140. doi: 10.1016/0014-5793(91)81360-k. [DOI] [PubMed] [Google Scholar]
  14. Hauser C., Saurat J. H., Schmitt A., Jaunin F., Dayer J. M. Interleukin 1 is present in normal human epidermis. J Immunol. 1986 May 1;136(9):3317–3323. [PubMed] [Google Scholar]
  15. Hazuda D. J., Lee J. C., Young P. R. The kinetics of interleukin 1 secretion from activated monocytes. Differences between interleukin 1 alpha and interleukin 1 beta. J Biol Chem. 1988 Jun 15;263(17):8473–8479. [PubMed] [Google Scholar]
  16. Holland K. T., Ingham E., Cunliffe W. J. A review, the microbiology of acne. J Appl Bacteriol. 1981 Oct;51(2):195–215. doi: 10.1111/j.1365-2672.1981.tb01234.x. [DOI] [PubMed] [Google Scholar]
  17. Ingham E., Eady E. A., Goodwin C. E., Cove J. H., Cunliffe W. J. Pro-inflammatory levels of interleukin-1 alpha-like bioactivity are present in the majority of open comedones in acne vulgaris. J Invest Dermatol. 1992 Jun;98(6):895–901. doi: 10.1111/1523-1747.ep12460324. [DOI] [PubMed] [Google Scholar]
  18. Jeremias J., Kalo-Klein A., Witkin S. S. Individual differences in tumour necrosis factor and interleukin-1 production induced by viable and heat-killed Candida albicans. J Med Vet Mycol. 1991;29(3):157–163. doi: 10.1080/02681219180000261. [DOI] [PubMed] [Google Scholar]
  19. Katsambas A., Antoniou C., Frangouli E., Avgerinou G., Michailidis D., Stratigos J. A double-blind trial of treatment of seborrhoeic dermatitis with 2% ketoconazole cream compared with 1% hydrocortisone cream. Br J Dermatol. 1989 Sep;121(3):353–357. doi: 10.1111/j.1365-2133.1989.tb01429.x. [DOI] [PubMed] [Google Scholar]
  20. Keddie F. M. Electron microscopy of Malassezia furfur in tinea versicolor. Sabouraudia. 1966 Oct;5(2):134–137. [PubMed] [Google Scholar]
  21. Kupper T. S., Ballard D. W., Chua A. O., McGuire J. S., Flood P. M., Horowitz M. C., Langdon R., Lightfoot L., Gubler U. Human keratinocytes contain mRNA indistinguishable from monocyte interleukin 1 alpha and beta mRNA. Keratinocyte epidermal cell-derived thymocyte-activating factor is identical to interleukin 1. J Exp Med. 1986 Dec 1;164(6):2095–2100. doi: 10.1084/jem.164.6.2095. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Kupper T. S., Chua A. O., Flood P., McGuire J., Gubler U. Interleukin 1 gene expression in cultured human keratinocytes is augmented by ultraviolet irradiation. J Clin Invest. 1987 Aug;80(2):430–436. doi: 10.1172/JCI113090. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. 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]
  24. Leeming J. P., Holland K. T., Cunliffe W. J. The microbial ecology of pilosebaceous units isolated from human skin. J Gen Microbiol. 1984 Apr;130(4):803–807. doi: 10.1099/00221287-130-4-803. [DOI] [PubMed] [Google Scholar]
  25. Leeming J. P., Notman F. H. Improved methods for isolation and enumeration of Malassezia furfur from human skin. J Clin Microbiol. 1987 Oct;25(10):2017–2019. doi: 10.1128/jcm.25.10.2017-2019.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Lindemann R. A., Economou J. S., Rothermel H. Production of interleukin-1 and tumor necrosis factor by human peripheral monocytes activated by periodontal bacteria and extracted lipopolysaccharides. J Dent Res. 1988 Aug;67(8):1131–1135. doi: 10.1177/00220345880670081401. [DOI] [PubMed] [Google Scholar]
  27. Luger T. A., Stadler B. M., Katz S. I., Oppenheim J. J. Epidermal cell (keratinocyte)-derived thymocyte-activating factor (ETAF). J Immunol. 1981 Oct;127(4):1493–1498. [PubMed] [Google Scholar]
  28. Marcon M. J., Powell D. A. Human infections due to Malassezia spp. Clin Microbiol Rev. 1992 Apr;5(2):101–119. doi: 10.1128/cmr.5.2.101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Mizutani H., Black R., Kupper T. S. Human keratinocytes produce but do not process pro-interleukin-1 (IL-1) beta. Different strategies of IL-1 production and processing in monocytes and keratinocytes. J Clin Invest. 1991 Mar;87(3):1066–1071. doi: 10.1172/JCI115067. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983 Dec 16;65(1-2):55–63. doi: 10.1016/0022-1759(83)90303-4. [DOI] [PubMed] [Google Scholar]
  31. Norris J. F., Cunliffe W. J. A histological and immunocytochemical study of early acne lesions. Br J Dermatol. 1988 May;118(5):651–659. doi: 10.1111/j.1365-2133.1988.tb02566.x. [DOI] [PubMed] [Google Scholar]
  32. Oppenheim J. J., Stadler B. M., Siraganian R. P., Mage M., Mathieson B. Lymphokines: their role in lymphocyte responses. Properties of interleukin 1. Fed Proc. 1982 Feb;41(2):257–262. [PubMed] [Google Scholar]
  33. Partridge M., Chantry D., Turner M., Feldmann M. Production of interleukin-1 and interleukin-6 by human keratinocytes and squamous cell carcinoma cell lines. J Invest Dermatol. 1991 May;96(5):771–776. doi: 10.1111/1523-1747.ep12471723. [DOI] [PubMed] [Google Scholar]
  34. Raponi G., Ghezzi M. C., Mancini C., Filadoro F. Preincubation of Candida albicans strains with amphotericin B reduces tumor necrosis factor alpha and interleukin-6 release by human monocytes. Antimicrob Agents Chemother. 1993 Sep;37(9):1958–1961. doi: 10.1128/aac.37.9.1958. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Roszkowski W., Roszkowski K., Ko H. L., Beuth J., Jeljaszewicz J. Immunomodulation by propionibacteria. Zentralbl Bakteriol. 1990 Dec;274(3):289–298. doi: 10.1016/s0934-8840(11)80686-9. [DOI] [PubMed] [Google Scholar]
  36. Sauder D. N., Carter C. S., Katz S. I., Oppenheim J. J. Epidermal cell production of thymocyte activating factor (ETAF). J Invest Dermatol. 1982 Jul;79(1):34–39. doi: 10.1111/1523-1747.ep12510569. [DOI] [PubMed] [Google Scholar]
  37. Takahashi M., Ushijima T., Ozaki Y. Biological activity of Pityrosporum. I. Enhancement of resistance in mice stimulated by Pityrosporum against Salmonella typhimurium. Immunology. 1984 Apr;51(4):697–702. [PMC free article] [PubMed] [Google Scholar]
  38. Takahashi M., Ushijima T., Ozaki Y. Biological activity of Pityrosporum. II. Antitumor and immune stimulating effect of Pityrosporum in mice. J Natl Cancer Inst. 1986 Nov;77(5):1093–1097. [PubMed] [Google Scholar]
  39. Timmerman C. P., Mattsson E., Martinez-Martinez L., De Graaf L., Van Strijp J. A., Verbrugh H. A., Verhoef J., Fleer A. Induction of release of tumor necrosis factor from human monocytes by staphylococci and staphylococcal peptidoglycans. Infect Immun. 1993 Oct;61(10):4167–4172. doi: 10.1128/iai.61.10.4167-4172.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Tokura Y., Edelson R. L., Gasparro F. P. Retinoid augmentation of bioactive interleukin-1 production by murine keratinocytes. Br J Dermatol. 1992 May;126(5):485–495. doi: 10.1111/j.1365-2133.1992.tb11823.x. [DOI] [PubMed] [Google Scholar]
  41. Whicher J., Ingham E. Cytokine measurements in body fluids. Eur Cytokine Netw. 1990 Oct-Nov;1(4):239–243. [PubMed] [Google Scholar]

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