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Up-regulation of HMGB1 and TLR4 in skin lesions of lichen planus

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Abstract

Lichen planus (LP) is a chronic, mucocutaneous inflammatory disease of an unknown aetiology. The disease has been associated with certain viruses, and the factors such as DAMPs (damage-associated molecular patterns) and PAMPs (pathogen-associated molecular patterns) may also contribute to the inflammatory response in LP. HMGB1 (high mobility group box 1 protein) is one of the major DAMPs that induces inflammation and could trigger LP disease. The present study was aimed to examine TLR4, RAGE and HMGB1 production in epidermis or dermis by immunohistochemistry and the respective expression of these targets in the skin lesions of patients with LP. Moreover, we measured HMGB1 serum levels by ELISA. The results showed similar profile of expression by HMGB1 and TLR4, which are decreased at epidermis and up-regulated at dermis of skin lesions of LP patients that was sustained by intense cellular infiltration. RAGE expression was also increased in dermis of LP. Although there is increased RAGE protein levels, a decreased RAGE transcript levels was detected. Similar HMGB1 serum levels were detected in the LP and control groups. This study demonstrates that HMGB1 and TLR4 could contribute to the inflammatory LP process in skin.

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Funding

This work was supported by the Fundação de Amparo à Pesquisa do Estado de São Paulo (2011/20740-3), the Laboratório de Investigação Médica, Unidade 56 do Hospital das Clínicas da Faculdade de Medicina de São Paulo and Fundo de Apoio à Dermatologia de São Paulo.

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Author notes

  1. Gabriel Costa de Carvalho and Fabiana Yasumoto Araujo Hirata contributed equally for this work.

Authors and Affiliations

  1. Laboratory of Dermatology and Immunodeficiencies, Medical School of the University of São Paulo, LIM-56, Av. Dr. Enéas de Carvalho Aguiar, 470, 3rd floor, São Paulo, 05403-000, Brazil

    Gabriel Costa de Carvalho, Fabiana Yasumoto Araujo Hirata, Rosana Domingues, Mariana Colombini Zaniboni, Naiura Vieira Pereira, Valéria Aoki, Alberto José da Silva Duarte & Maria Notomi Sato

  2. Institute of Adolfo Lutz, Respiratory Infectious Diseases, São Paulo, Brazil

    Cristina Adelaide Figueiredo

  3. Department of Pathology, University of São Paulo Medical School, São Paulo, Brazil

    Mirian Nacagami Sotto & Alberto José da Silva Duarte

Authors
  1. Gabriel Costa de Carvalho
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  2. Fabiana Yasumoto Araujo Hirata
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  3. Rosana Domingues
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  4. Cristina Adelaide Figueiredo
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  5. Mariana Colombini Zaniboni
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  6. Naiura Vieira Pereira
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  7. Mirian Nacagami Sotto
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  8. Valéria Aoki
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  9. Alberto José da Silva Duarte
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  10. Maria Notomi Sato
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Corresponding author

Correspondence to Maria Notomi Sato.

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The authors have no conflicts of interest to declare.

Ethical approval

All experiments were approved by the local medical ethics committee prior to the study.

Informed consent

Written informed consent was obtained from all patients before inclusion in the study.

Additional information

Cristina Adelaide Figueiredo—in memoriam.

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de Carvalho, G.C., Hirata, F.Y.A., Domingues, R. et al. Up-regulation of HMGB1 and TLR4 in skin lesions of lichen planus. Arch Dermatol Res 310, 523–528 (2018). https://doi.org/10.1007/s00403-018-1837-5

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  • DOI: https://doi.org/10.1007/s00403-018-1837-5

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