title: Interferon-inducible T-cell alpha chemoattractant (ITAC) induces the melanocytic migration and hypopigmentation through destabilizing p53 via histone deacetylase 5: a possible role of ITAC in pigment-related disorders.
abstract: BACKGROUND
  Cell migration plays a major role in the immune response and in tumorigenesis. Interferon-inducible T-cell alpha chemoattractant (ITAC) elicits a strong chemotactic response from immune cells.
  
  
  OBJECTIVE
  To examine the effect of ITAC on melanocyte migration and pigmentation and its involvement in related disorders, and to investigate potential key players in these processes.
  
  
  METHODS
  Human melanocytes or melanoma cells were treated with ITAC and a migration assay was carried out. Global gene expression analysis was performed to find genes regulated by ITAC treatment. The function of key players involved in ITAC-induced cellular processes was addressed using knockdown or overexpression experiments in combination with ITAC treatment. ITAC expression in the inflammation-associated hypopigmentary disorder, vitiligo, was examined.
  
  
  RESULTS
  Among CXCR3 ligands, only ITAC induced melanocyte migration. ITAC treatment upregulated the expression of histone deacetylase 5 (HDAC5) and downregulated that of p53, a known target of HDAC5. Through knockdown or overexpression of HDAC5 and p53, we confirmed that HDAC5 mediates ITAC-induced migration by decreasing levels of p53 via deacetylation. In addition, ITAC treatment could decrease pigmentation in a p53- and HDAC5-dependent manner. Finally, the increased migration of human melanoma cells by ITAC treatment and the increased ITAC expression in the epidermis of vitiligo skin were verified.
  
  
  CONCLUSIONS
  This study provides in vitro evidence for the migratory and hypopigmentation effects of ITAC on melanocytic cells, gives translational insights into the roles of ITAC in pathological conditions, and suggests that HDAC5 and its substrate p53 are potent targets for regulating ITAC-induced cellular processes.
authors.affiliation: Basic Research & Innovation Division, R&D Unit, AmorePacific Corporation, Yongin-si, Gyeonggi-do, Republic of Korea.
authors.forename: E
authors.initials: E
authors.lastname: Lee
authors.affiliation: Basic Research & Innovation Division, R&D Unit, AmorePacific Corporation, Yongin-si, Gyeonggi-do, Republic of Korea.
authors.forename: S-Y
authors.initials: SY
authors.lastname: Choi
authors.affiliation: Basic Research & Innovation Division, R&D Unit, AmorePacific Corporation, Yongin-si, Gyeonggi-do, Republic of Korea.
authors.forename: B-H
authors.initials: BH
authors.lastname: Bin
authors.affiliation: Department of Dermatology, Dongguk University Ilsan Hospital, Goyang-si, Gyeonggi-do, Republic of Korea.
authors.forename: N-H
authors.initials: NH
authors.lastname: Kim
authors.affiliation: Basic Research & Innovation Division, R&D Unit, AmorePacific Corporation, Yongin-si, Gyeonggi-do, Republic of Korea.
authors.forename: K H
authors.initials: KH
authors.lastname: Kim
authors.affiliation: Gyeonggi Bio Center, Gyeonggi Institute of Science & Technology Promotion, Suwon-si, Gyeonggi-do, Republic of Korea.
authors.forename: D-H
authors.initials: DH
authors.lastname: Choi
authors.affiliation: Basic Research & Innovation Division, R&D Unit, AmorePacific Corporation, Yongin-si, Gyeonggi-do, Republic of Korea.
authors.forename: J
authors.initials: J
authors.lastname: Han
authors.affiliation: Basic Research & Innovation Division, R&D Unit, AmorePacific Corporation, Yongin-si, Gyeonggi-do, Republic of Korea.
authors.forename: H
authors.initials: H
authors.lastname: Choi
authors.affiliation: Department of Dermatology, Dongguk University Ilsan Hospital, Goyang-si, Gyeonggi-do, Republic of Korea.
authors.forename: A-Y
authors.initials: AY
authors.lastname: Lee
authors.affiliation: Basic Research & Innovation Division, R&D Unit, AmorePacific Corporation, Yongin-si, Gyeonggi-do, Republic of Korea.
authors.forename: T R
authors.initials: TR
authors.lastname: Lee
authors.affiliation: Basic Research & Innovation Division, R&D Unit, AmorePacific Corporation, Yongin-si, Gyeonggi-do, Republic of Korea.
authors.forename: E-G
authors.initials: EG
authors.lastname: Cho
mesh_terms: D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D054371:Chemokine CXCL11 / Q000494:pharmacology*; D015536:Down-Regulation / Q000502:physiology; D000078404:Epidermal Cells; D055785:Gene Knockdown Techniques; D006655:Histone Deacetylases / Q000172:deficiency / Q000378:metabolism*; D006801:Humans; D017496:Hypopigmentation / Q000201:enzymology*; D008544:Melanocytes / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism; D054387:Receptors, CXCR / Q000378:metabolism; D012097:Repressor Proteins / Q000172:deficiency; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology
chemical_list: D054371:Chemokine CXCL11; D012333:RNA, Messenger; D054387:Receptors, CXCR; D012097:Repressor Proteins; D016159:Tumor Suppressor Protein p53; C404500:HDAC5 protein, human; C486544:HDAC9 protein, human; D006655:Histone Deacetylases