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Front. Pharmacol. | doi: 10.3389/fphar.2018.00067

Tacrolimus reverses UVB irradiation-induced epidermal Langerhans cell reduction by inhibiting TNF-α secretion in keratinocytes via regulation of NF-κB/p65

 JiaLi Xu1, YaDong Feng1, GuoXing Song1, QiXing Gong1, Li Yin1, YingYing Hu1, Dan Luo1 and  Zhiqiang Yin1*
  • 1First Affiliated Hospital, Nanjing Medical University, China

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 pimecrolimus 1% cream could reverse high-dose ultraviolet B (UVB) irradiation-induced epidermal Langerhans cells (LCs) reduction via inhibition of LCs 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 4 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: 0h, 18 h, 24h, and 48h. 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 4 groups: Control, Tacrolimus (1ug/ml), UVB (30mJ/cm2), and UVB (30mJ/cm2)+ Tacrolimus (1ug/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 LCs reduction and CD1a+ cells 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 receptorⅡ: IgG Fc fusion protein) could significantly reverse UVB irradiation-induced epidermal LCs reduction.
Conclusion: Topical tacrolimus 0.03% could reverse UVB irradiation-induced epidermal LCs reduction by inhibiting TNF-α secretion in keratinocytes via regulation of NF-κB/p65.

Keywords: Tacrolimus, UVB, Langerhans Cells, TNF-α, NF-κB

Received: 30 Nov 2017; Accepted: 18 Jan 2018.

Edited by:

Timothy J. Keane, Imperial College London, United Kingdom

Reviewed by:

Claudio Ferrante, Università degli Studi G. d'Annunzio Chieti e Pescara, Italy
Lucia Recinella, Università degli Studi G. d'Annunzio Chieti e Pescara, Italy  

Copyright: © 2018 Xu, Feng, Song, Gong, Yin, Hu, Luo and Yin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Zhiqiang Yin, First Affiliated Hospital, Nanjing Medical University, Nanjing, China, yzq2802@sina.com