AUTHOR=Xu JiaLi , Feng YaDong , Song GuoXin , Gong QiXing , Yin Li , Hu YingYing , Luo Dan , Yin ZhiQiang 

TITLE=Tacrolimus Reverses UVB Irradiation-Induced Epidermal Langerhans Cell Reduction by Inhibiting TNF-α Secretion in Keratinocytes via Regulation of NF-κB/p65

JOURNAL=Frontiers in Pharmacology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2018.00067

DOI=10.3389/fphar.2018.00067

ISSN=1663-9812

ABSTRACT=<p><bold>Background:</bold> 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.</p><p><bold>Methods:</bold> Twenty fresh human foreskin tissues were randomly divided into four groups as follows: <italic>Control</italic>, <italic>Tacrolimus</italic> (0.03%), <italic>UVB</italic> (180 mJ/cm<sup>2</sup>), <italic>and UVB</italic> (180 mJ/cm<sup>2</sup>) + <italic>Tacrolimus</italic> (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: <italic>Control</italic>, <italic>Tacrolimus</italic> (1 μg/ml), <italic>UVB</italic> (30 mJ/cm<sup>2</sup>), <italic>and UVB</italic> (30 mJ/cm<sup>2</sup>) + <italic>Tacrolimus</italic> (1 μg/ml). The cells were incubated for 24 h and prepared for real-time quantitative PCR and western blot.</p><p><bold>Results:</bold> 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.</p><p><bold>Conclusion:</bold> 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.</p>