Abstract
Background: Topical calcineurin inhibitors including tacrolimus and pimecrolimus are used in the treatment of many inflammatory skin diseases mainly via blocking T-cell proliferation. Our previous studies found that pimecrolimus 1% cream could reverse high-dose ultraviolet B (UVB) irradiation-induced epidermal Langerhans cell (LC) reduction via inhibition of LC migration. We conducted this study to investigate the effects of topical tacrolimus 0.03% ointment on high-dose UVB-irradiated human epidermal LCs.Methods: Twenty fresh human foreskin tissues were randomly divided into four groups as follows: Control, Tacrolimus (0.03%), UVB (180 mJ/cm2), and UVB (180 mJ/cm2) + Tacrolimus (0.03%). Four time points were set as follows: 0, 18, 24, and 48 h. We collected culture medium and tissues at each time point. The percentage of CD1a+ cells in the medium was detected by means of flow cytometry. Each tissue was prepared for immunohistochemistry, real-time quantitative PCR, and western blot. HaCaT cells were cultured and divided into four groups: Control, Tacrolimus (1 μg/ml), UVB (30 mJ/cm2), and UVB (30 mJ/cm2) + Tacrolimus (1 μg/ml). The cells were incubated for 24 h and prepared for real-time quantitative PCR and western blot.Results: Topical tacrolimus significantly reversed high-dose UVB irradiation-induced epidermal LC reduction and CD1a+ cell increment in culture medium. Tacrolimus significantly inhibited UVB irradiation-induced tumor necrosis factor-α (TNF-α) and nuclear factor kappa B (NF-κB)/p65 mRNA and protein expression in HaCaT cells. Tacrolimus also significantly inhibited high-dose UVB irradiation-induced TNF-α expression in cultured tissues. Finally, TNF-α antagonist (recombinant human TNF-α receptor II: IgG Fc fusion protein) could significantly reverse UVB irradiation-induced epidermal LC reduction.Conclusion: Topical tacrolimus 0.03% could reverse UVB irradiation-induced epidermal LC reduction by inhibiting TNF-α secretion in keratinocytes via regulation of NF-κB/p65.
Highlights
Topical calcineurin inhibitors (TCIs), including tacrolimus ointment and pimecrolimus cream, are widely used in the treatment of atopic dermatitis and many other inflammatory skin diseases, where the central therapeutic mechanism is to block T-cell proliferation and inhibit the activation of T-cells and thereby diminish inflammation (Yin et al, 2014; Nygaard et al, 2017)
Our previous studies found that pimecrolimus 1% cream could reverse high-dose ultraviolet B (UVB) irradiation-induced epidermal Langerhans cell (LC) reduction via inhibition of Langerhans cells (LCs) migration
This study aimed to investigate the effect of topical tacrolimus 0.03% ointment on high-dose UVB-irradiated human epidermal LCs and the possible relation with tumor necrosis factor-α (TNF-α) secretion and NF-kB/p65 regulation, which would contribute to further understanding of the mechanism of TCI action and treatment
Summary
Topical calcineurin inhibitors (TCIs), including tacrolimus ointment and pimecrolimus cream, are widely used in the treatment of atopic dermatitis and many other inflammatory skin diseases, where the central therapeutic mechanism is to block T-cell proliferation and inhibit the activation of T-cells and thereby diminish inflammation (Yin et al, 2014; Nygaard et al, 2017). Single high-dose ultraviolet B (UVB) irradiation can induce significant epidermal LC depletion in human skin, and the increased migration of LCs might be the main mechanism (Kölgen et al, 2002). Our previous studies found that pimecrolimus 1% cream could reverse high-dose ultraviolet B (UVB) irradiation-induced epidermal Langerhans cell (LC) reduction via inhibition of LC migration. We conducted this study to investigate the effects of topical tacrolimus 0.03% ointment on high-dose UVB-irradiated human epidermal LCs
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