title: Tumor necrosis factor-alpha decreases aquaporin-3 expression in DJM-1 keratinocytes.
abstract: Aquaporin-3 (AQP3) is a water/glycerol-transporting protein that is strongly expressed at the plasma membranes of keratinocytes in skin. There is evidence for involvement of AQP3-facilitated water and glycerol transport in skin hydration and wound repair, respectively. In this study, we show that tumor necrosis factor-alpha (TNF-alpha) and TNF receptor-1 signaling decreased AQP3 protein expression and plasma membrane water permeability in DJM-1 keratinocytes. TNF-alpha also decreased AQP3 mRNA expression and promoter activity, indicating that TNF-alpha suppresses AQP3 gene transcription. In addition, inhibitors of p38 and extracellular signal-regulated kinase (ERK) abolished the effect of TNF-alpha on AQP3 expression level, whereas inhibitors for NF-kappaB did not. These data indicate that TNF-alpha decreases AQP3 gene expression through p38 and ERK activation, and suggest that the decrease in AQP3 expression caused by TNF-alpha might be related to the phenotypes of skin inflammation, such as dry skin.
authors.affiliation: Department of Chemico-Pharmacological Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Horie
authors.forename: Mamiko
authors.initials: M
authors.lastname: Maeda
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yokoyama
authors.forename: Akinori
authors.initials: A
authors.lastname: Hisatsune
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Katsuki
authors.forename: Takeshi
authors.initials: T
authors.lastname: Miyata
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Isohama
mesh_terms: D051400:Aquaporin 3 / Q000096:biosynthesis* / Q000235:genetics; D002460:Cell Line; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005786:Gene Expression Regulation; D005990:Glycerol / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D020871:RNA Stability; D012333:RNA, Messenger / Q000096:biosynthesis; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism* / Q000494:pharmacology; D014867:Water / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: C496027:AQP3 protein, human; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D014867:Water; D051400:Aquaporin 3; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D005990:Glycerol