title: Follistatin-like protein 1 modulates IL-17 signaling via IL-17RC regulation in stromal cells.
abstract: Follistatin-like protein 1 (FSTL-1) possesses several newly identified roles in mammalian biology, including interleukin (IL)-17-driven inflammation, though the mechanism underlying FSTL-1 influence on IL-17-mediated cytokine production is unknown. Using parallel in vitro bone marrow stromal cell models of FSTL-1 suppression, we employed unbiased microarray analysis to identify FSTL-1-regulated genes and pathways that could influence IL-17-dependent production of IL-6 and granulocyte colony-stimulating factor. We discovered that FSTL-1 modulates Il17rc gene expression. Specifically, FSTL-1 was necessary for Il17rc gene transcription, IL-17RC surface protein expression and IL-17-dependent cytokine production. This work identifies a mechanism by which FSTL-1 influences IL-17-driven inflammatory signaling in vitro and reveals a novel function for FSTL-1, as a modulator of gene expression. Thus enhanced understanding of the interplay between FSTL-1 and IL-17-mediated inflammation may provide insight into potential therapeutic targets of IL-17-mediated diseases and warrants ongoing study of in vivo models and clinical scenarios of FSTL-1-influenced diseases.
authors.affiliation: Division of Pediatric Infectious Diseases, Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.|Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, USA.|Richard K Mellon Institute for Pediatric Research, Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: Brian T
authors.initials: BT
authors.lastname: Campfield
authors.affiliation: Richard K Mellon Institute for Pediatric Research, Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: Taylor
authors.initials: T
authors.lastname: Eddens
authors.affiliation: Division of Pediatric Infectious Diseases, Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.|Richard K Mellon Institute for Pediatric Research, Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Henkel
authors.affiliation: Division of Pediatric Infectious Diseases, Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.|Richard K Mellon Institute for Pediatric Research, Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Majewski
authors.affiliation: Richard K Mellon Institute for Pediatric Research, Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: William
authors.initials: W
authors.lastname: Horne
authors.affiliation: Stead Family Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, IA, USA.
authors.forename: Yury
authors.initials: Y
authors.lastname: Chaly
authors.affiliation: Division of Rheumatology &Clinical Immunology, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Gaffen
authors.affiliation: Stead Family Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, IA, USA.
authors.forename: Raphael
authors.initials: R
authors.lastname: Hirsch
authors.affiliation: Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, USA.|Richard K Mellon Institute for Pediatric Research, Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: Jay K
authors.initials: JK
authors.lastname: Kolls
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D046149:Embryo Culture Techniques; D038702:Follistatin-Related Proteins / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D055786:Gene Knockout Techniques; D007249:Inflammation / Q000235:genetics; D020381:Interleukin-17 / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics*; D034741:RNA, Small Interfering / Q000235:genetics; D018123:Receptors, Interleukin / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D038702:Follistatin-Related Proteins; C448720:Fstl1 protein, mouse; C508527:Il17rc protein, mouse; D020381:Interleukin-17; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D018123:Receptors, Interleukin