title: Aquaporin 5 increases keratinocyte-derived chemokine expression and NF-κB activity through ERK activation.
abstract: Aquaporin-5 (AQP5) is a water-selective channel protein that is expressed in submucosal glands and alveolar epithelial cells in the lungs. Recent studies have revealed that AQPs regulate not only water metabolism, but also some cellular functions such as cell growth and migration. Here, we report the role of AQP5 in inflammatory responses. In MLE-12 cells, knockdown of AQP5 using siRNA (10-50 nM) attenuated TNF-α-induced expression of keratinocyte chemoattractant (KC) mRNA and protein. Conversely, in NIH-3T3 cells, overexpression of AQP5 increased KC expression, NF-κB activation, and ERK phosphorylation. The AQP5-induced increase of KC expression was diminished by treatment with ERK inhibitors. Taken together, we propose a new function of AQP5 as an inflammatory signal potentiator, which may be mediated by increased activation of ERK and NF-κB.
authors.affiliation: Department of Chemico-Pharmacological Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-Honmachi, Kumamoto 862-0973, Japan; Laboratory of Applied Pharmacology, Faculty of Pharmaceutical Sciences, Tokyo University of Sciences, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
authors.forename: Yuima
authors.initials: Y
authors.lastname: Sakamoto
authors.affiliation: Department of Chemico-Pharmacological Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-Honmachi, Kumamoto 862-0973, Japan.
authors.forename: Akinori
authors.initials: A
authors.lastname: Hisatsune
authors.affiliation: Department of Chemico-Pharmacological Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-Honmachi, Kumamoto 862-0973, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Katsuki
authors.affiliation: Laboratory of Applied Pharmacology, Faculty of Pharmaceutical Sciences, Tokyo University of Sciences, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Horie
authors.affiliation: Laboratory of Applied Pharmacology, Faculty of Pharmaceutical Sciences, Tokyo University of Sciences, 2641 Yamazaki, Noda, Chiba 278-8510, Japan. Electronic address: isohama@rs.tus.ac.jp.
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Isohama
mesh_terms: D056809:Alveolar Epithelial Cells / Q000378:metabolism; D000818:Animals; D051402:Aquaporin 5 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D054360:Chemokine CXCL1 / Q000235:genetics / Q000378:metabolism; D018925:Chemokines / Q000235:genetics* / Q000378:metabolism*; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D007249:Inflammation / Q000378:metabolism; D015603:Keratinocytes / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D041681:NIH 3T3 Cells; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C496038:Aqp5 protein, mouse; D051402:Aquaporin 5; D054360:Chemokine CXCL1; D018925:Chemokines; C475895:Cxcl1 protein, mouse; D016328:NF-kappa B; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D014409:Tumor Necrosis Factor-alpha
keywords: Aquaporin 5; Keratinocyte chemoattractant; TNF-α