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Effects of mammalian target of rapamycin inhibitors on cytokine production and differentiation in keratinocytes
Author(s) -
DeTemple Viola,
Satzger Imke,
Walter Antje,
Schaper Katrin,
Gutzmer Ralf
Publication year - 2016
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/exd.13079
Subject(s) - cytokine , microbiology and biotechnology , keratinocyte , chemistry , immunology , cancer research , biology , biochemistry , in vitro
Risk factors for the development of cutaneous squamous cell carcinoma (c SCC ) include ultraviolet radiation and immunosuppression. In particular, solid organ transplant recipients show a high incidence of c SCC , depending on the immunosuppressive regimen. While azathioprine or calcineurin inhibitors increase the risk of c SCC development, mammalian target of rapamycin (m TOR ) inhibitors decreases this risk. At the moment, the mechanisms behind this protective effect of m TOR inhibitors are not fully understood. We evaluated effects of the m TOR inhibitors sirolimus and everolimus on keratinocytes, c SCC cell lines and an organotypic skin model in vitro in regard to proliferation, cytokine secretion and differentiation. We show that m TOR inhibitors block keratinocyte proliferation and alter cytokine and cytokeratin production: in particular, m TOR inhibition leads to upregulation of interleukin‐6 and downregulation of cytokeratin 10. Therefore, m TOR inhibitors have effects on keratinocytes, which could play a role in the pathogenesis of c SCC .