Cyclosporin A (CsA), an immunosuppressant, is known to exhibit hypertrichosis as a side effect. This compound prolongs human hair growth in a hair follicle organ culture system. Thus, CsA has anagen-prolonging activity, but the mechanism of the action is unclear. In immunosuppression, CsA binds to cyclophilin (CyP) to form a complex that inhibits the activity of a phosphatase, calcineurin (CaN), which in turn inhibits the nuclear translocation of NFAT, a transcription factor involved in the expression of IL-2 and other proteins. The purpose of this study was to determine how CsA causes hypertrichosis. In this study, the cultured human dermal papilla cells (DPCs) were used. These cells were cultured in 10% FBS-DMEM (Thermo Fisher Scientific) as a basic condition. Cells were cultured at 37°C in a humidified atmosphere containing 5% carbon dioxide gas. When assessing the effect of CsA on the gene expression, DPCs were cultured in the medium without FBS. Gene expression analysis was carried out by PCR and real-time PCR, and these experiments were performed with rTaq (Toyobo) or SYBR qPCR mix (Toyobo). CsA was used as a CaN inhibitor, and VIVIT (Cayman Chemical) as a NFAT inhibitor. By using PCR, it was evaluated that the seven isoforms of CyP were expressed in the DPCs. Real-time PCR experiments revealed that CyP-A and CyP-B accounted for approximately 98% of the expressed CyPs. In the DPCs, expressions of all isoforms of NFAT and CaN were confirmed by PCR. Addition of CsA to cultured DPCs decreased TGF-β2 expression. The same result was obtained when VIVIT was added. From these results, CsA prolongs anagen by decreasing TGF-β2 expression in DPCs. Furthermore, CyPs, CaNs, and NFATs, key molecules involved in immunosuppressive mechanisms, were expressed in DPCs. Based on the results, the intracellular signaling of CsA to suppress TGF-β2 expression in DPCs might be similar to that of immunosuppression.

ESDR563 - CsA-induced hypertrichosis might be caused in part by inhibition of TGF-β2 expression in dermal papilla cells.

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