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Research Letters | Feb 2013

Influence of Cyclosporin and Prednisolone on RAGE, S100A8/A9, and NFκB Expression in Human Keratinocytes

Nadia Djerbi, MD; Piotr J. Dziunycz, MD; Dominic Reinhardt, MD; Guergana Iotzova-Weiss, PhD; Jürg Hafner, MD; Severin Läuchli, MD; Lars E. French, MD; Günther F. L. Hofbauer, MD

JAMA Dermatol. 2013;149(2):236-237. doi:10.1001/jamadermatol.2013.836.

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Squamous cell carcinoma (SCC) is the most common neoplasm among immunosuppressed patients.¹ The immune system plays a prominent role in tumor development. The role of RAGE and its extracellular heterodimeric ligand S100A8/A9 in the development of SCC has recently been suggested.² Because this pathway acts through the transcription factor NFκB and thus regulates inflammatory responses, its function may be of particular interest with respect to the development of skin cancer in immunosuppressed patients. Therefore, we aimed to analyze the impact of the most commonly used immunosuppressive agents (cyclosporin A and prednisolone) on RAGE, S100A8/A9, and NFkB expression.

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Figure 1. Methylprednisolone (MP) induced increased expression of several genes in cultured normal human keratinocytes. A and B, Real-time polymerase chain reaction analysis of messenger RNA (mRNA) showed up to 5-fold increased S100A8 expression (A) and up to 2-fold S100A9 expression (B) after 12 hours of incubation in different MP concentrations. C and D, In addition, MP upregulated the mRNA levels of RAGE by 3-fold (C) and NFκB up to 14-fold (D) in a dose-dependent manner. The graphs show mean (SD) relative expression. * P < .05; † P < .01; ‡ P < .001.

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Figure 2. Cyclosporin A (CsA) in various concentrations was applied to cultured normal human keratinocytes. A-D, Concentrations of CsA from 1μM to 10μM were applied to human primary keratinocytes for 12 hours, and thereafter, messenger RNA (mRNA) extraction and real-time polymerase chain reaction analysis was performed. After 12 hours of CsA incubation S100A8 (A) and S100A9 (B) mRNA levels were increased. The expression of RAGE mRNA was slightly but significantly decreased (C), while the expression of NFκB remained unchanged (D). The graphs show mean (SD) relative expression. * P < .05; † P < .01.

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Djerbi N, Dziunycz PJ, Reinhardt D, et al. Influence of Cyclosporin and Prednisolone on RAGE, S100A8/A9, and NFκB Expression in Human Keratinocytes. JAMA Dermatol. 2013;149(2):236-237. doi:10.1001/jamadermatol.2013.836.

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Influence of Cyclosporin and Prednisolone on RAGE, S100A8/A9, and NFκB Expression in Human Keratinocytes

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