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. 1995 Oct;86(2):244–249.

Induced expression of mRNA for IL-5, IL-6, TNF-alpha, MIP-2 and IFN-gamma in immunologically activated rat peritoneal mast cells: inhibition by dexamethasone and cyclosporin A.

C M Williams 1, J W Coleman 1
PMCID: PMC1384002  PMID: 7490125

Abstract

We examined the capacity of purified rat peritoneal connective tissue-type mast cells (PMC) to express mRNA for several cytokines. Stimulation of PMC with anti-IgE for 4 hr induced the expression of mRNA encoding interleukin-5 (IL-5), IL-6, tumour necrosis factor-alpha (TNF-alpha), macrophage inflammatory protein-2 (MIP-2) and interferon-gamma (IFN-gamma). Unstimulated PMC expressed detectable mRNA for TNF-alpha but not for the other four cytokines. Incubation of PMC with cyclosporin A (CsA) or dexamethasone (DEX), each at 10(-6) M for 24 hr, significantly inhibited the induced expression of mRNA for each of the five cytokines, and also inhibited release of biologically active TNF-alpha. Throughout these experiments mRNA levels of the housekeeping gene G3PDH were not altered by stimulation with anti-IgE or incubation with CsA or DEX. We conclude that immunological activation of rat PMC induces gene expression of several cytokines and that expression of these genes can be inhibited by immunosuppressive drugs.

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Selected References

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

  1. Amano Y., Lee S. W., Allison A. C. Inhibition by glucocorticoids of the formation of interleukin-1 alpha, interleukin-1 beta, and interleukin-6: mediation by decreased mRNA stability. Mol Pharmacol. 1993 Feb;43(2):176–182. [PubMed] [Google Scholar]
  2. Barnes P. J., Chung K. F., Page C. P. Inflammatory mediators and asthma. Pharmacol Rev. 1988 Mar;40(1):49–84. [PubMed] [Google Scholar]
  3. Benyon R. C., Bissonnette E. Y., Befus A. D. Tumor necrosis factor-alpha dependent cytotoxicity of human skin mast cells is enhanced by anti-IgE antibodies. J Immunol. 1991 Oct 1;147(7):2253–2258. [PubMed] [Google Scholar]
  4. Bissonnette E. Y., Hogaboam C. M., Wallace J. L., Befus A. D. Potentiation of tumor necrosis factor-alpha-mediated cytotoxicity of mast cells by their production of nitric oxide. J Immunol. 1991 Nov 1;147(9):3060–3065. [PubMed] [Google Scholar]
  5. Bradding P., Feather I. H., Howarth P. H., Mueller R., Roberts J. A., Britten K., Bews J. P., Hunt T. C., Okayama Y., Heusser C. H. Interleukin 4 is localized to and released by human mast cells. J Exp Med. 1992 Nov 1;176(5):1381–1386. doi: 10.1084/jem.176.5.1381. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bradding P., Roberts J. A., Britten K. M., Montefort S., Djukanovic R., Mueller R., Heusser C. H., Howarth P. H., Holgate S. T. Interleukin-4, -5, and -6 and tumor necrosis factor-alpha in normal and asthmatic airways: evidence for the human mast cell as a source of these cytokines. Am J Respir Cell Mol Biol. 1994 May;10(5):471–480. doi: 10.1165/ajrcmb.10.5.8179909. [DOI] [PubMed] [Google Scholar]
  7. Brown M. A., Pierce J. H., Watson C. J., Falco J., Ihle J. N., Paul W. E. B cell stimulatory factor-1/interleukin-4 mRNA is expressed by normal and transformed mast cells. Cell. 1987 Aug 28;50(5):809–818. doi: 10.1016/0092-8674(87)90339-4. [DOI] [PubMed] [Google Scholar]
  8. Buckley M. G., Williams C. M., Thompson J., Pryor P., Ray K., Butterfield J. H., Coleman J. W. IL-4 enhances IL-3 and IL-8 gene expression in a human leukemic mast cell line. Immunology. 1995 Mar;84(3):410–415. [PMC free article] [PubMed] [Google Scholar]
  9. Burd P. R., Rogers H. W., Gordon J. R., Martin C. A., Jayaraman S., Wilson S. D., Dvorak A. M., Galli S. J., Dorf M. E. Interleukin 3-dependent and -independent mast cells stimulated with IgE and antigen express multiple cytokines. J Exp Med. 1989 Jul 1;170(1):245–257. doi: 10.1084/jem.170.1.245. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Fort P., Marty L., Piechaczyk M., el Sabrouty S., Dani C., Jeanteur P., Blanchard J. M. Various rat adult tissues express only one major mRNA species from the glyceraldehyde-3-phosphate-dehydrogenase multigenic family. Nucleic Acids Res. 1985 Mar 11;13(5):1431–1442. doi: 10.1093/nar/13.5.1431. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Ghiara P., Boraschi D., Villa L., Scapigliati G., Taddei C., Tagliabue A. In vitro generated mast cells express natural cytotoxicity against tumour cells. Immunology. 1985 Jun;55(2):317–324. [PMC free article] [PubMed] [Google Scholar]
  12. Gordon J. R., Galli S. J. Mast cells as a source of both preformed and immunologically inducible TNF-alpha/cachectin. Nature. 1990 Jul 19;346(6281):274–276. doi: 10.1038/346274a0. [DOI] [PubMed] [Google Scholar]
  13. Gordon J. R., Galli S. J. Release of both preformed and newly synthesized tumor necrosis factor alpha (TNF-alpha)/cachectin by mouse mast cells stimulated via the Fc epsilon RI. A mechanism for the sustained action of mast cell-derived TNF-alpha during IgE-dependent biological responses. J Exp Med. 1991 Jul 1;174(1):103–107. doi: 10.1084/jem.174.1.103. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hatfield S. M., Roehm N. W. Cyclosporine and FK506 inhibition of murine mast cell cytokine production. J Pharmacol Exp Ther. 1992 Feb;260(2):680–688. [PubMed] [Google Scholar]
  15. Huang S., Paulauskis J. D., Godleski J. J., Kobzik L. Expression of macrophage inflammatory protein-2 and KC mRNA in pulmonary inflammation. Am J Pathol. 1992 Oct;141(4):981–988. [PMC free article] [PubMed] [Google Scholar]
  16. Humphries R. K., Abraham S., Krystal G., Lansdorp P., Lemoine F., Eaves C. J. Activation of multiple hemopoietic growth factor genes in Abelson virus-transformed myeloid cells. Exp Hematol. 1988 Oct;16(9):774–781. [PubMed] [Google Scholar]
  17. Kaye R. E., Fruman D. A., Bierer B. E., Albers M. W., Zydowsky L. D., Ho S. I., Jin Y. J., Castells M. C., Schreiber S. L., Walsh C. T. Effects of cyclosporin A and FK506 on Fc epsilon receptor type I-initiated increases in cytokine mRNA in mouse bone marrow-derived progenitor mast cells: resistance to FK506 is associated with a deficiency in FK506-binding protein FKBP12. Proc Natl Acad Sci U S A. 1992 Sep 15;89(18):8542–8546. doi: 10.1073/pnas.89.18.8542. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Leal-Berumen I., Conlon P., Marshall J. S. IL-6 production by rat peritoneal mast cells is not necessarily preceded by histamine release and can be induced by bacterial lipopolysaccharide. J Immunol. 1994 Jun 1;152(11):5468–5476. [PubMed] [Google Scholar]
  19. Marshall J. S., Gauldie J., Nielsen L., Bienenstock J. Leukemia inhibitory factor production by rat mast cells. Eur J Immunol. 1993 Sep;23(9):2116–2120. doi: 10.1002/eji.1830230911. [DOI] [PubMed] [Google Scholar]
  20. Murphy P. M. The molecular biology of leukocyte chemoattractant receptors. Annu Rev Immunol. 1994;12:593–633. doi: 10.1146/annurev.iy.12.040194.003113. [DOI] [PubMed] [Google Scholar]
  21. Möller A., Lippert U., Lessmann D., Kolde G., Hamann K., Welker P., Schadendorf D., Rosenbach T., Luger T., Czarnetzki B. M. Human mast cells produce IL-8. J Immunol. 1993 Sep 15;151(6):3261–3266. [PubMed] [Google Scholar]
  22. Noble A., Staynov D. Z., Diaz-Sanchez D., Lee T. H., Kemeny D. M. Elimination of IgE regulatory rat CD8+ T cells in vivo increases the co-ordinate expression of Th2 cytokines IL-4, IL-5 and IL-10. Immunology. 1993 Oct;80(2):326–329. [PMC free article] [PubMed] [Google Scholar]
  23. Northemann W., Braciak T. A., Hattori M., Lee F., Fey G. H. Structure of the rat interleukin 6 gene and its expression in macrophage-derived cells. J Biol Chem. 1989 Sep 25;264(27):16072–16082. [PubMed] [Google Scholar]
  24. Plaut M., Pierce J. H., Watson C. J., Hanley-Hyde J., Nordan R. P., Paul W. E. Mast cell lines produce lymphokines in response to cross-linkage of Fc epsilon RI or to calcium ionophores. Nature. 1989 May 4;339(6219):64–67. doi: 10.1038/339064a0. [DOI] [PubMed] [Google Scholar]
  25. Rolfe F. G., Hughes J. M., Armour C. L., Sewell W. A. Inhibition of interleukin-5 gene expression by dexamethasone. Immunology. 1992 Dec;77(4):494–499. [PMC free article] [PubMed] [Google Scholar]
  26. Selvan R. S., Butterfield J. H., Krangel M. S. Expression of multiple chemokine genes by a human mast cell leukemia. J Biol Chem. 1994 May 13;269(19):13893–13898. [PubMed] [Google Scholar]
  27. Sillaber C., Bevec D., Butterfield J. H., Heppner C., Valenta R., Scheiner O., Kraft D., Lechner K., Bettelheim P., Valent P. Tumor necrosis factor alpha and interleukin-1 beta mRNA expression in HMC-1 cells: differential regulation of gene product expression by recombinant interleukin-4. Exp Hematol. 1993 Aug;21(9):1271–1275. [PubMed] [Google Scholar]
  28. Smith T. J., Ducharme L. A., Weis J. H. Preferential expression of interleukin-12 or interleukin-4 by murine bone marrow mast cells derived in mast cell growth factor or interleukin-3. Eur J Immunol. 1994 Apr;24(4):822–826. doi: 10.1002/eji.1830240408. [DOI] [PubMed] [Google Scholar]
  29. Waage A., Slupphaug G., Shalaby R. Glucocorticoids inhibit the production of IL6 from monocytes, endothelial cells and fibroblasts. Eur J Immunol. 1990 Nov;20(11):2439–2443. doi: 10.1002/eji.1830201112. [DOI] [PubMed] [Google Scholar]
  30. Walsh L. J., Trinchieri G., Waldorf H. A., Whitaker D., Murphy G. F. Human dermal mast cells contain and release tumor necrosis factor alpha, which induces endothelial leukocyte adhesion molecule 1. Proc Natl Acad Sci U S A. 1991 May 15;88(10):4220–4224. doi: 10.1073/pnas.88.10.4220. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Wershil B. K., Furuta G. T., Lavigne J. A., Choudhury A. R., Wang Z. S., Galli S. J. Dexamethasone or cyclosporin A suppress mast cell-leukocyte cytokine cascades. Multiple mechanisms of inhibition of IgE- and mast cell-dependent cutaneous inflammation in the mouse. J Immunol. 1995 Feb 1;154(3):1391–1398. [PubMed] [Google Scholar]
  32. Wodnar-Filipowicz A., Heusser C. H., Moroni C. Production of the haemopoietic growth factors GM-CSF and interleukin-3 by mast cells in response to IgE receptor-mediated activation. Nature. 1989 May 11;339(6220):150–152. doi: 10.1038/339150a0. [DOI] [PubMed] [Google Scholar]
  33. Young J. D., Liu C. C., Butler G., Cohn Z. A., Galli S. J. Identification, purification, and characterization of a mast cell-associated cytolytic factor related to tumor necrosis factor. Proc Natl Acad Sci U S A. 1987 Dec;84(24):9175–9179. doi: 10.1073/pnas.84.24.9175. [DOI] [PMC free article] [PubMed] [Google Scholar]

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