title: Retinoic acid and hydroquinone induce inverse expression patterns on cornified envelope-associated proteins: implication in skin irritation.
abstract: BACKGROUND
  Hydroquinone (HQ) with or without retinoic acid (RA) is routinely used for the treatment of hyperpigmented conditions. Skin irritation is a major problem with popular depigmenting agents, resulting in postinflammatory hyperpigmentation.
  
  
  OBJECTIVE
  To examine the molecular mechanism associated with skin irritation by RA or HQ.
  
  
  METHODS
  A genome-wide transcriptional profiling analysis was performed using monolayer cultures of human keratinocytes treated with or without irritant doses of RA, HQ, or sodium lauryl sulfate (SLS), a representative irritant. Differentially expressed genes (DEGs) were mapped on human chromosomes using a Manhattan plot. For the validation of candidate DEGs, the chemicals with different concentrations of varying irritation intensities were applied in vitro and in vivo and analyzed using real time-PCR and Western blotting.
  
  
  RESULTS
  DEGs mapped to the 1q21 locus, which is composed of a cluster of genes encoding the cornified envelope precursors, showed an inverse expression pattern in response to HQ and RA. Concentrations of RA and HQ that induced a broad range of irritant responses in cultured cells or mice skin also induced inverse effects on the expression of cornified envelope-associated proteins.
  
  
  CONCLUSIONS
  Genetic modulation on cornified envelope-associated proteins by RA-induced irritation, which may be involved in physiological skin barrier disturbance, could be inverse to that by HQ- or SLS-induced irritation.
authors.affiliation: Department of Dermatology, Dongguk University Ilsan Hospital, Graduate School of Medicine, 814 Siksa-dong, Ilsandong-gu, Goyang-si, Gyeonggi-do 410-773, South Korea.
authors.forename: Kyung Ah
authors.initials: KA
authors.lastname: Cheong
authors.affiliation: Department of Dermatology, Dongguk University Ilsan Hospital, Graduate School of Medicine, 814 Siksa-dong, Ilsandong-gu, Goyang-si, Gyeonggi-do 410-773, South Korea.
authors.forename: Ha Jung
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Dermatology, Dongguk University Ilsan Hospital, Graduate School of Medicine, 814 Siksa-dong, Ilsandong-gu, Goyang-si, Gyeonggi-do 410-773, South Korea.
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Department of Dermatology, Dongguk University Ilsan Hospital, Graduate School of Medicine, 814 Siksa-dong, Ilsandong-gu, Goyang-si, Gyeonggi-do 410-773, South Korea.
authors.forename: Chang-Hyun
authors.initials: CH
authors.lastname: Kim
authors.affiliation: Department of Dermatology, Dongguk University Ilsan Hospital, Graduate School of Medicine, 814 Siksa-dong, Ilsandong-gu, Goyang-si, Gyeonggi-do 410-773, South Korea.
authors.forename: Won-Suk
authors.initials: WS
authors.lastname: Lim
authors.affiliation: Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 152-742, South Korea. Electronic address: minsoonoh@snu.ac.kr.
authors.forename: Minsoo
authors.initials: M
authors.lastname: Noh
authors.affiliation: Department of Dermatology, Dongguk University Ilsan Hospital, Graduate School of Medicine, 814 Siksa-dong, Ilsandong-gu, Goyang-si, Gyeonggi-do 410-773, South Korea. Electronic address: leeay@duih.org.
authors.forename: Ai-Young
authors.initials: AY
authors.lastname: Lee
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002878:Chromosomes, Human, Pair 1; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D006873:Hydroquinones / Q000494:pharmacology*; D007509:Irritants / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D012967:Sodium Dodecyl Sulfate / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: D006873:Hydroquinones; D007509:Irritants; D012967:Sodium Dodecyl Sulfate; D014212:Tretinoin; C031927:hydroquinone
keywords: Cornified envelope-associated proteins; Hydroquinone; Inverse modulation; Irritation; Retinoic acid