title: Novel approaches to vitiligo treatment via modulation of mTOR and NF-κB pathways in human skin melanocytes.
abstract: Vitiligo is a skin depigmentation disorder with an increasing prevalence. Among recognized mechanisms is the oxidative stress that affects melanocytes which are responsible for skin pigmentation. Studies have shown that high concentration of hydrogen peroxide, or H2O2, induces apoptotic activities. Few studies have been done with lower doses of H2O2. Using human skin melanocytes, we investigated the effect of moderate concentration of H2O2on melanocyte dendrites. Confocal data show that H2O2at 250 µM induces loss of dendrites, as indicated by cytoskeletal proteins. α-melanocyte stimulating hormone or α-MSH pretreatment protects against H2O2-induced loss of dendrites, while α-MSH alone enhances dendrites. PI3K/AKT inhibitor LY294002 and mTORC1 inhibitor Rapamycin inhibit α-MSH-induced dendrites. In this study, we also investigated the effect of TNFα on cultured human skin melanocytes, since TNFα plays important roles in vitiligo. Confocal data demonstrate that TNFα induces NFκB activation. Western blot analysis shows that TNFα induces IκB phosphorylation and degradation. Interestingly, α-MSH does not have any effect of TNFα-induced IκB degradation and NF-κB activation. α-MSH, however, activates mTORC1 pathway. TNFα induces p38 but not AMPKα activation. Collectively, our data suggest that modulation of mTOR and NF-κB pathways may be a novel approach for better clinical management of vitiligo.
authors.affiliation: Department of Biology, Providence College, Providence, RI 02918, USA.
authors.forename: Jerry
authors.initials: J
authors.lastname: Wan
authors.affiliation: Department of Dermatology, the 3 rd Hospital of Hangzhou, Hangzhou 310000, Zhejiang Province, China.
authors.forename: Fuquan
authors.initials: F
authors.lastname: Lin
authors.affiliation: Department of Dermatology, Guiyang Medical University, Guizhou 550004, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Dermatology, the 3 rd Hospital of Hangzhou, Hangzhou 310000, Zhejiang Province, China.
authors.forename: Aie
authors.initials: A
authors.lastname: Xu
authors.affiliation: Department of Biology, Providence College, Providence, RI 02918, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: DeGiorgis
authors.affiliation: Department of Dermatology, Guiyang Medical University, Guizhou 550004, China.
authors.forename: Hongguang
authors.initials: H
authors.lastname: Lu
authors.affiliation: Department of Biology, Providence College, Providence, RI 02918, USA.
authors.forename: Yinsheng
authors.initials: Y
authors.lastname: Wan
mesh_terms: D015153:Blotting, Western; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008544:Melanocytes / Q000187:drug effects* / Q000378:metabolism*; D018613:Microscopy, Confocal; D009025:Morpholines / Q000494:pharmacology / Q000627:therapeutic use; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D020123:Sirolimus / Q000494:pharmacology / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology / Q000627:therapeutic use; D014820:Vitiligo / Q000188:drug therapy / Q000378:metabolism*; D000521:alpha-MSH / Q000494:pharmacology
chemical_list: D002867:Chromones; D006861:Hydrogen Peroxide; D009025:Morpholines; D016328:NF-kappa B; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D020123:Sirolimus; D058570:TOR Serine-Threonine Kinases; D014409:Tumor Necrosis Factor-alpha; D000521:alpha-MSH; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
keywords: TNFα; mTORC1; vitiligo; α-MSH