Effect of cytokines and ultraviolet B radiation on the promoter activity of the metallothionein gene in keratinocytes

Abstract

Metallothionein (MT) has many functions that are modulated by several factors, including ultraviolet (UV) radiation and cytokines. We thought that these diverse functions of MT might reflect the specific regulatory mechanisms of its expression. To understand some of the molecular mechanisms underlying MT expression, we examined the effects of several cytokines and UVB on the promoter activity of the MT gene. First, we introduced the MT promoter construct into the HaCaT keratinocytes and treated them with various concentrations of interleukin-1α (IL-1α) and IL-6. The addition of IL-1α and IL-6 led to an increase in the promoter activity of the MT gene. UVB is known to induce MT expression in epidermal keratinocytes, and IL-6 is a possible mediator of MT induction by UV radiation. Therefore, we investigated whether UVB could induce MT promoter activity. Our results showed, interestingly, that UVB radiation has no or little effect on the promoter activity. This suggested a complex molecular regulation of the MT gene.

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Narumi, H. , Nakano, H. , Kaneko, T. , Nakajima, K. , Matsuzaki, Y. , Aizu, T. , Sawamura, D. and Hanada, K. (2013) Effect of cytokines and ultraviolet B radiation on the promoter activity of the metallothionein gene in keratinocytes. Advances in Bioscience and Biotechnology, 4, 896-899. doi: 10.4236/abb.2013.49117.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1] Masters, B.A., Kelly, E.J., Quaife, C.J., Brinster, R.L. and Palmiter, R.D. (1994) Targeted disruption of metallothionein I and II genes increases sensitivity to cadmium. Proceedings of the National Academy of Sciences of the United States of America, 91, 584-588. doi:10.1073/pnas.91.2.584
[2] Lazo, J.S., Kondo, Y., Dellapiazza, D., Michalska, A.E., Choo, K.H. and Pitt, B.R. (1995) Enhanced sensitivity to oxidative stress in cultured embryonic cells from transgenic mice deficient in metallothionein I and II genes. Journal of Biological Chemistry, 270, 5506-5510. doi:10.1074/jbc.270.10.5506
[3] Hanada, K., Sawamura, D., Tamai, K., Baba, T., Hashimoto, I., Muramatsu, T., Miura, N. and Naganuma, A. (1998) Novel function of metallothionein in photoprotection: Metallothionein-null mouse exhibits reduced tolerance against ultraviolet B injury in the skin. Journal of Investigative Dermatology, 111, 582-585. doi:10.1046/j.1523-1747.1998.00342.x
[4] Angel, P., Poting, A., Mallick, U., Rahmsdorf, H.J., Schorpp, M. and Herrlich, P. (1986) Induction of metallothionein and other mRNA species by carcinogens and tumor promoters in primary human skin fibroblasts. Molecular and Cellular Biology, 6, 1760-1766.
[5] Shiraishi, N., Yamamoto, H., Takeda, Y., Kondoh, S., Hayashi, H., Hashimoto, K. and Aono, K. (1986) Increased metallothionein content in rat liver and kidney following X-irradiation. Toxicology and Applied Pharmacology, 85, 128-134. doi:10.1016/0041-008X(86)90106-7
[6] Baba, T., Nakano, H., Tamai, K., Sawamura, D., Hanada, K., Hashimoto, I. and Arima, Y. (1998) Inhibitory effect of beta-thujaplicin on ultraviolet B-induced apoptosis in mouse keratinocytes. Journal of Investigative Dermatology, 110, 24-28. doi:10.1046/j.1523-1747.1998.00078.x
[7] Sato, M., Sasaki, M. and Hojo, H. (1994) Differential induction of metallothionein synthesis by interleukin-6 and tumor necrosis factor-alpha in rat tissues. International Journal of Immunopharmacology, 16, 187-195. doi:10.1016/0192-0561(94)90075-2
[8] Nakano, H., Ikenaga, S., Aizu, T., Kaneko, T., Matsuzaki, Y., Tsuchida, S., Hanada, K. and Arima, Y. (2006) Human metallothionein gene expression is upregulated by beta-thujaplicin: Possible involvement of protein kinase C and reactive oxygen species. Biological and Pharmaceutical Bulletin, 29, 55-59. doi:10.1248/bpb.29.55
[9] Hanada, K. (2000) Photoprotective role of metallothionein in UV-injury-metallothionein-null mouse exhibits reduced tolerance against ultraviolet-B. Journal of Dermatological Science, 23, S51-S56. doi:10.1016/S0923-1811(99)00078-X
[10] Goldbach-Mansky, R. and Kastner, D.L. (2009) Autoinflammation: The prominent role of IL-1 in monogenic autoinflammatory diseases and implications for common illnesses. Journal of Allergy and Clinical Immunology, 124, 1141-1149. doi:10.1016/j.jaci.2009.11.016
[11] Sawamura, D., Meng, X., Ina, S., Sato, M., Tamai, K., Hanada, K. and Hashimoto, I. (1998) Induction of keratinocyte proliferation and lymphocytic infiltration by in vivo introduction of the IL-6 gene into keratinocytes and possibility of keratinocyte gene therapy for inflammatory skin diseases using IL-6 mutant genes. Journal of Immunology, 161, 5633-5639.
[12] Vicentini, F.T., He, T., Shao, Y., Fonseca, M.J.V., Verri Jr., W.A., Fisher, G.J. and Xu, Y. (2011) Quercetin inhibits UV irradiation-induced inflammatory cytokine production in primary human keratinocytes by suppressing NF-κB pathway. Journal of Dermatological Science, 61, 162-168. doi:10.1016/j.jdermsci.2011.01.002
[13] Nishimura, N., Reeve, V.E., Nishimura, H., Satoh, M. and Tohyama, C. (2000) Cutaneous metallothionein induction by ultraviolet B irradiation in interleukin-6 null mice. Journal of Investigative Dermatology, 114, 343-348. doi:10.1046/j.1523-1747.2000.00862.x

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