Abstract
Environmental estrogens or estrogen disrupters have recently received a great deal of attention because of their potential health impact on reproductive tissues. Few, if any, studies have been made on the impact of these compounds on the immune system. We sought to determine the activities of various environmental estrogens on the modulation of the interleukin-1β (IL-1β) gene in a model monocytic cell line, hER+IL-1β-CAT+. This cell line stably transfected with the human estrogen receptor, and an IL-1β promoter construct fused to the CAT reporter gene allows us to monitor the effect of estrogenic compounds on IL-1β promoter activity. 17β-Estradiol (E2) markedly enhanced lipopolysaccharide-(LPS) induced IL-1β promoter-driven CAT activity in a dose-dependent manner. The mycotoxins α-zearalenol and zearalenone both exhibited full agonist activity, but at lower potencies, with EC50 values of 1.8 and 54 nM, respectively, compared with E2 at 0.5 nM. In addition, genistein was a very low-potency agonist, having an EC50 of 1.5 µM. Similar to the E2 response, the slope factors for α-zearalenol, zearalenone, and genistein were close to 3.0, suggesting positive cooperativity in the estrogenic response. The activity of the mycotoxins appeared to be mediated through the estrogen receptor, since both the antiestrogens H1285 and ICI 182,780 effectively inhibited their agonist activity in a dose-dependent manner. Representative environmental estrogenic compounds both from plant and industrial sources were also tested. Unlike the mycoestrogens, none of the compounds, with the exception of genistein, synergized with LPS to enhance IL-1β promoter activity. When tested for antiestrogenic activity, the industrial compound 4-octylphenol was able to antagonize the response to E2; however, the response was three orders of magnitude less potent than H1285. Naringenin, a plant flavonoid, showed little or no ability to antagonize the response to E2. Overall, the results show that some environmental estrogens that display agonist activity in reproductive tissue also have an effect on IL-1 gene expression in hemopoietic-derived tissue.
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References
Feldman, D. (1997). Endocrinology 138, 1777–1779.
Raloff, J. (1993). Sci. News 144, 10–13.
Collins, B. M., McLachlan, J. A., and Arnold, S. F. (1997). Steroids 62, 365–372.
Miksicek, R. J. (1993). Mol. Pharmacol. 44, 37–43.
Nagel, S. C., vom Saal, F. S., Thayer, K. A., Dhar, M. G., Boechler, M., and Welshons, W. V. (1997). Environ. Health Perspect. 105, 70–76.
Ruh, M. F., Bi, Y., D’Alonzo, R., and Bellone, C. J. (1998). J. Steroid Biochem. Mol. Biol. 66, 203–210.
Ruh, T. S., Baudendistel, L. J., Nicholson, W. F., and Ruh, M. F. (1979). J. Steroid Biochem. 11, 315–322.
Wakeling, A. E. and Bowler, J. (1988). J. Steroid Biochem. 30, 141–148.
Pacifici, R. (1996). J. Bone Miner. Res. 11, 1043–1051.
Pivirotto, L. A., Cissel, D. S., and Keeting, P. E. (1995). Mol. Cell. Endocrinol. 111, 67–74.
Li, Z. G., Danis, V. A., and Brooks, P. M. (1993). Clin. Exp. Rheum. 11, 157–162.
Yang, N. N., Venugopalan, M., Hardikar, S., and Glasebrook, A. (1996). Science 273, 1222–1225.
Messina, M. and Barnes, S. (1991). J. Natl. Cancer Inst. 83, 541–546.
Adlercreutz, H., Mousavi, Y., Clark, J., Hockerstedt, K., Hamalainen, E., Wahala, K., et al. (1992). J. Steroid Biochem. Mol. Biol. 41, 331–337.
Katzenellenbogen, B. S., Katzenellenbogen, J. A., and Mordecai, D. (1979). Endocrinology 105, 33–40.
Hagler, W. M., Mirocha, C. J., Pathre, S. V., and Behrens, J. C. (1979). Appl. Environ. Microb. 37, 849–853.
Mastri, C., Mistry, P., and Lucier, G. W. (1985). J. Steroid Biochem. 23, 279–289.
Ruh, M. F., Zacharewski, T., Connor, K., Howell, J., Chen, I., and Safe, S. (1995). Biochem. Pharm. 50, 1485–1493.
Akiyama, T., Ishida, J., Nakagawa, S., Ogawata, H., Watanabe, S.-I., Itoh, N., et al. (1987). J. Biol. Chem. 262, 5592–5595.
Miksicek, R. J. (1994). J. Steroid Biochem. Mol. Biol. 49, 153–160.
Godambe, S. A., Chaplin, D. D., Takova, T., and Bellone, C. J. (1994). J. Immunol. 153, 143–152.
Korea, H. S., Handwereger, B. S., and Wunderlich, J. R. (1975). J. Immunol. 114, 894.
Kushner, P. J., Hort, E., Shine, J., Baxter, J. D., and Greene, G. L. (1990). Mol. Endocrinol. 4, 1465–1473.
Tora, L., Mullick, A., Metzger, D., Ponglikitmongkol, M., Park, I., and Chambon, P. (1989). EMBO J. 8, 1981–1986.
Seed, B. and Sheen, J. Y. (1988). Gene 67, 271–277.
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Ruh, M.F., Bi, Y., Cox, L. et al. Effect of environmental estrogens on IL-1β promoter activity in a macrophage cell line. Endocr 9, 207–211 (1998). https://doi.org/10.1385/ENDO:9:2:207
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DOI: https://doi.org/10.1385/ENDO:9:2:207