Effects of mammalian target of rapamycin inhibitors on cytokine production and differentiation in keratinocytes
| Autor: | Antje Walter, Katrin Schaper, Imke Satzger, Viola DeTemple, Ralf Gutzmer |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Keratinocytes Dermatology Biochemistry 03 medical and health sciences 0302 clinical medicine Interleukin 20 Downregulation and upregulation Cell Line Tumor medicine Humans Molecular Biology PI3K/AKT/mTOR pathway Cell Proliferation Everolimus business.industry TOR Serine-Threonine Kinases RPTOR Cell Differentiation Calcineurin 030104 developmental biology 030220 oncology & carcinogenesis Sirolimus Immunology Cancer research Cytokines Cytokine secretion business medicine.drug |
| Zdroj: | Experimental dermatology. 25(10) |
| ISSN: | 1600-0625 |
| Popis: | Risk factors for the development of cutaneous squamous cell carcinoma (cSCC) include ultraviolet radiation and immunosuppression. In particular, solid organ transplant recipients show a high incidence of cSCC, depending on the immunosuppressive regimen. While azathioprine or calcineurin inhibitors increase the risk of cSCC development, mammalian target of rapamycin (mTOR) inhibitors decreases this risk. At the moment, the mechanisms behind this protective effect of mTOR inhibitors are not fully understood. We evaluated effects of the mTOR inhibitors sirolimus and everolimus on keratinocytes, cSCC cell lines and an organotypic skin model in vitro in regard to proliferation, cytokine secretion and differentiation. We show that mTOR inhibitors block keratinocyte proliferation and alter cytokine and cytokeratin production: in particular, mTOR inhibition leads to upregulation of interleukin-6 and downregulation of cytokeratin 10. Therefore, mTOR inhibitors have effects on keratinocytes, which could play a role in the pathogenesis of cSCC. |
| Databáze: | OpenAIRE |
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