Skip to main content
Infection and Immunity logoLink to Infection and Immunity
. 1990 Nov;58(11):3564–3567. doi: 10.1128/iai.58.11.3564-3567.1990

Mycoplasmas induce transcription and production of tumor necrosis factor in a monocytic cell line, THP-1, by a protein kinase C-independent pathway.

K Sugama 1, K Kuwano 1, M Furukawa 1, Y Himeno 1, T Satoh 1, S Arai 1
PMCID: PMC313698  PMID: 2228228

Abstract

We demonstrated that mycoplasmas (MP), previously shown to augment the antitumor activity of murine peritoneal macrophages, also induce cytotoxic activity in a human monocytic cell line, THP-1. THP-1 cells were induced to produce cytotoxic activity by MP in a time- and dose-dependent manner. By using neutralization by antibody against tumor necrosis factor (TNF), the cytotoxic activity was shown to be due to TNF released from the MP-stimulated cells. Studies with inhibitors of second-messenger pathways and Northern RNA blot analysis indicated that a Ca2(+)-dependent, but not protein kinase C-dependent, biochemical pathway is involved in MP-induced TNF production by THP-1 cells and that MP induce TNF production in the cells at the level of transcription. MP, unlike other bacteria, lack cell walls and lipopolysaccharide. The possible involvement of a TNF production mechanism distinct from that triggered by lipopolysaccharide is discussed.

Full text

PDF
3564

Images in this article

Selected References

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

  1. Armstrong C. A., Klostergaard J., Granger G. A. Isolation and initial characterization of tumoricidal monokine(s) from the human monocytic leukemia cell line THP-1. J Natl Cancer Inst. 1985 Jan;74(1):1–9. [PubMed] [Google Scholar]
  2. Beutler B., Cerami A. Cachectin and tumour necrosis factor as two sides of the same biological coin. Nature. 1986 Apr 17;320(6063):584–588. doi: 10.1038/320584a0. [DOI] [PubMed] [Google Scholar]
  3. Burchett S. K., Weaver W. M., Westall J. A., Larsen A., Kronheim S., Wilson C. B. Regulation of tumor necrosis factor/cachectin and IL-1 secretion in human mononuclear phagocytes. J Immunol. 1988 May 15;140(10):3473–3481. [PubMed] [Google Scholar]
  4. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  5. Gallily R., Sher T., Ben-Av P., Loewenstein J. Tumor necrosis factor as a mediator of Mycoplasma orale-induced tumor cell lysis by macrophages. Cell Immunol. 1989 Jun;121(1):146–153. doi: 10.1016/0008-8749(89)90012-9. [DOI] [PubMed] [Google Scholar]
  6. Hampton R. Y., Golenbock D. T., Raetz C. R. Lipid A binding sites in membranes of macrophage tumor cells. J Biol Chem. 1988 Oct 15;263(29):14802–14807. [PubMed] [Google Scholar]
  7. Hayflick L. Tissue cultures and mycoplasmas. Tex Rep Biol Med. 1965 Jun;23(Suppl):285+–285+. [PubMed] [Google Scholar]
  8. Hidaka H., Inagaki M., Kawamoto S., Sasaki Y. Isoquinolinesulfonamides, novel and potent inhibitors of cyclic nucleotide dependent protein kinase and protein kinase C. Biochemistry. 1984 Oct 9;23(21):5036–5041. doi: 10.1021/bi00316a032. [DOI] [PubMed] [Google Scholar]
  9. Hidaka H., Sasaki Y., Tanaka T., Endo T., Ohno S., Fujii Y., Nagata T. N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide, a calmodulin antagonist, inhibits cell proliferation. Proc Natl Acad Sci U S A. 1981 Jul;78(7):4354–4357. doi: 10.1073/pnas.78.7.4354. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Himeno Y., Fukuda Y., Hatanaka M., Imura H. Expression of oncogenes in human liver disease. Liver. 1988 Aug;8(4):208–212. doi: 10.1111/j.1600-0676.1988.tb00994.x. [DOI] [PubMed] [Google Scholar]
  11. Holian A., Jordan M. K., Nguyen H. V., Devenyi Z. J. Inhibition of macrophage activation by isoquinolinesulfonamides, phenothiazines, and a napthalenesulfonamide. J Cell Physiol. 1988 Oct;137(1):45–54. doi: 10.1002/jcp.1041370106. [DOI] [PubMed] [Google Scholar]
  12. Introna M., Hamilton T. A., Kaufman R. E., Adams D. O., Bast R. C., Jr Treatment of murine peritoneal macrophages with bacterial lipopolysaccharide alters expression of c-fos and c-myc oncogenes. J Immunol. 1986 Oct 15;137(8):2711–2715. [PubMed] [Google Scholar]
  13. Isakov N., Mally M. I., Scholz W., Altman A. T-lymphocyte activation: the role of protein kinase C and the bifurcating inositol phospholipid signal transduction pathway. Immunol Rev. 1987 Feb;95:89–111. doi: 10.1111/j.1600-065x.1987.tb00501.x. [DOI] [PubMed] [Google Scholar]
  14. Kiener P. A., Marek F., Rodgers G., Lin P. F., Warr G., Desiderio J. Induction of tumor necrosis factor, IFN-gamma, and acute lethality in mice by toxic and non-toxic forms of lipid A. J Immunol. 1988 Aug 1;141(3):870–874. [PubMed] [Google Scholar]
  15. Kovacs E. J., Radzioch D., Young H. A., Varesio L. Differential inhibition of IL-1 and TNF-alpha mRNA expression by agents which block second messenger pathways in murine macrophages. J Immunol. 1988 Nov 1;141(9):3101–3105. [PubMed] [Google Scholar]
  16. Larsson L. G., Ivhed I., Gidlund M., Pettersson U., Vennström B., Nilsson K. Phorbol ester-induced terminal differentiation is inhibited in human U-937 monoblastic cells expressing a v-myc oncogene. Proc Natl Acad Sci U S A. 1988 Apr;85(8):2638–2642. doi: 10.1073/pnas.85.8.2638. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Mitchell R. L., Zokas L., Schreiber R. D., Verma I. M. Rapid induction of the expression of proto-oncogene fos during human monocytic differentiation. Cell. 1985 Jan;40(1):209–217. doi: 10.1016/0092-8674(85)90324-1. [DOI] [PubMed] [Google Scholar]
  18. Nakamura T., Hemmi H., Aso H., Ishida N. Variants of a human monocytic leukemia cell line (THP-1): induction of differentiation by retinoic acid, interferon-gamma, and T-lymphocyte-derived differentiation-inducing activity. J Natl Cancer Inst. 1986 Jul;77(1):21–27. [PubMed] [Google Scholar]
  19. Philip R., Epstein L. B. Tumour necrosis factor as immunomodulator and mediator of monocyte cytotoxicity induced by itself, gamma-interferon and interleukin-1. Nature. 1986 Sep 4;323(6083):86–89. doi: 10.1038/323086a0. [DOI] [PubMed] [Google Scholar]
  20. Renz H., Gong J. H., Schmidt A., Nain M., Gemsa D. Release of tumor necrosis factor-alpha from macrophages. Enhancement and suppression are dose-dependently regulated by prostaglandin E2 and cyclic nucleotides. J Immunol. 1988 Oct 1;141(7):2388–2393. [PubMed] [Google Scholar]
  21. Takeda K., Iwamoto S., Sugimoto H., Takuma T., Kawatani N., Noda M., Masaki A., Morise H., Arimura H., Konno K. Identity of differentiation inducing factor and tumour necrosis factor. 1986 Sep 25-Oct 1Nature. 323(6086):338–340. doi: 10.1038/323338a0. [DOI] [PubMed] [Google Scholar]
  22. Tannenbaum C. S., Koerner T. J., Jansen M. M., Hamilton T. A. Characterization of lipopolysaccharide-induced macrophage gene expression. J Immunol. 1988 May 15;140(10):3640–3645. [PubMed] [Google Scholar]
  23. Tsuchiya S., Kobayashi Y., Goto Y., Okumura H., Nakae S., Konno T., Tada K. Induction of maturation in cultured human monocytic leukemia cells by a phorbol diester. Cancer Res. 1982 Apr;42(4):1530–1536. [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES