title: PHF11 expression and cellular distribution is regulated by the Toll-Like Receptor 3 Ligand Polyinosinic:Polycytidylic Acid in HaCaT keratinocytes.
abstract: BACKGROUND
  Inflammatory skin diseases such as atopic dermatitis and psoriasis represent a complex interaction between the skin and infiltrating immune cells, resulting in damage to the skin barrier and increased inflammation. Polymorphisms in PHF11 have been associated with dermatitis and allergy and PHF11 regulates the transcription of T-cell cytokines as well as class switching to IgE in activated B-cells. The importance of skin barrier homeostasis in the context of inflammatory skin diseases, together with reports identifying PHF11 as an interferon-induced gene, have led us to examine its role in the innate immune response of keratinocytes.
  
  
  RESULTS
  We developed a cell culture model that allowed us to analyze the effects of the double-stranded RNA analogue poly(I:C) on a confluent cell monolayer immediately after a 24-h treatment, as well as three days after withdrawal of treatment. Immediately after treatment with poly(I:C), PHF11, IL8, and interferon-dependent ISG15 RNA expression was increased. This was accompanied by nuclear localization of PHF11 as well the tight junction protein claudin-1. Knock-down of PHF11 resulted in increased interleukin-8 expression and secretion immediately following treatment with poly(I:C), as well as changes in the cellular distribution of membrane-bound and increased nuclear claudin-1 that was observed up to 3 days after the withdrawal of poly(I:C). This was associated with lower cell density and a decrease in the number of cells in the G1 phase of the cell cycle.
  
  
  CONCLUSIONS
  In addition to a role for PHF11 in lymphocyte gene expression, we have now shown that PHF11 was part of the keratinocyte innate immune response by poly(I:C). As knock-down of PHF11 was associated with increased expression of the pro-inflammatory chemokine IL-8 and changes in the cellular distribution of claudin-1, a change normally associated with increased proliferation and migration, we suggest that PHF11 may contribute to epidermal recovery following infection or other damage.
authors.affiliation: School of Science and Health, Western Sydney University, Locked Bag 1797, 2751, Penrith, NSW, Australia. P.Muscat@westernsydney.edu.au.
authors.forename: Pauline
authors.initials: P
authors.lastname: Muscat
authors.affiliation: School of Science and Health, Western Sydney University, Locked Bag 1797, 2751, Penrith, NSW, Australia. K.Mercado@westernsydney.edu.au.
authors.forename: Karessa
authors.initials: K
authors.lastname: Mercado
authors.affiliation: Present address: Garvan Institute for Medical Research, Darlinghurst, NSW, Australia. k.payne@garvan.org.au.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Payne
authors.affiliation: School of Science and Health, Western Sydney University, Locked Bag 1797, 2751, Penrith, NSW, Australia. cha_hal@hotmail.com.
authors.forename: Hardip
authors.initials: H
authors.lastname: Chahal
authors.affiliation: School of Science and Health, Western Sydney University, Locked Bag 1797, 2751, Penrith, NSW, Australia. graham.jones@uws.edu.au.
authors.forename: Graham
authors.initials: G
authors.lastname: Jones
mesh_terms: D000595:Amino Acid Sequence; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D015870:Gene Expression; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D055785:Gene Knockdown Techniques; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism*; D008024:Ligands; D008969:Molecular Sequence Data; D009154:Mutation; D011070:Poly I-C / Q000494:pharmacology*; D054730:Protein Interaction Domains and Motifs / Q000235:genetics; D021381:Protein Transport / Q000187:drug effects; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D051196:Toll-Like Receptor 3 / Q000378:metabolism*; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D014162:Transfection
chemical_list: D004268:DNA-Binding Proteins; D008024:Ligands; C493258:PHF11 protein, human; D034741:RNA, Small Interfering; D051196:Toll-Like Receptor 3; D014157:Transcription Factors; D011070:Poly I-C