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IL-17 sequestration via salivary gland gene therapy in a mouse model of Sjogren's syndrome suppresses disease-associated expression of the putative autoantigen Klk1b22.
Wu, Changgong; Wang, Zhimin; Zourelias, Lee; Thakker, Hiteshi; Passineau, Michael J.
Afiliación
  • Wu C; Gene Therapy Program, Department of Medicine, Division of Cardiovascular Medicine, Allegheny Health Network, Room 841, South Tower, 320 East North Avenue, Pittsburgh, PA, 15212-4772, USA. cw1@wpahs.org.
  • Wang Z; Gene Therapy Program, Department of Medicine, Division of Cardiovascular Medicine, Allegheny Health Network, Room 841, South Tower, 320 East North Avenue, Pittsburgh, PA, 15212-4772, USA. zwang1@wpahs.org.
  • Zourelias L; Gene Therapy Program, Department of Medicine, Division of Cardiovascular Medicine, Allegheny Health Network, Room 841, South Tower, 320 East North Avenue, Pittsburgh, PA, 15212-4772, USA. lzoureli@wpahs.org.
  • Thakker H; Gene Therapy Program, Department of Medicine, Division of Cardiovascular Medicine, Allegheny Health Network, Room 841, South Tower, 320 East North Avenue, Pittsburgh, PA, 15212-4772, USA. hiteshi.s.thakker@gmail.com.
  • Passineau MJ; Gene Therapy Program, Department of Medicine, Division of Cardiovascular Medicine, Allegheny Health Network, Room 841, South Tower, 320 East North Avenue, Pittsburgh, PA, 15212-4772, USA. mpassine@wpahs.org.
Arthritis Res Ther ; 17: 198, 2015 Aug 06.
Article en En | MEDLINE | ID: mdl-26245278
INTRODUCTION: IL-17 has a putative role in the pathophysiology of Sjogren's syndrome (SS) and has been shown to be upregulated in the salivary glands of affected individuals. Sequestration of IL-17 with Adenoviral-mediated gene therapy has previously shown a benefit upon the SS-like phenotype in the Aec1/Aec2 mouse model. We sought to understand the proteomic consequences of IL-17 sequestration in the salivary gland of this mouse model as a means of illuminating the role of IL-17 in SS-like disease. METHODS: Ultrasound-assisted gene transfer (UAGT) was utilized to express a fusion protein composed of the extracellular portion of the IL-17 receptor fused to fragment of crystallization (Fc) in the submandibular glands of Aec1/Aec2 mice at 8 weeks of age. After confirming expression of the fusion protein and local and systemic sequestration of IL-17, proteomic profiling was performed on submandibular glands of a treated cohort of Aec1/Aec2 animals relative to the background strain and sham-treated animals. RESULTS: The most notable proteomic signatures of IL-17 sequestration on SS-like disease-related proteins were Kallikrein-related peptidases, including the putative autoantigen Klk1b22. IL-17 sequestration also notably led to an isoelectric shift, but not a molecular weight shift, of Kallikrein-1, attributed to phosphorylation. CONCLUSION: Non-viral IL-17 sequestration gene therapy in the salivary gland is feasible and downregulates expression of a putative SS autoantigen in the Aec1/Aec2 mouse.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Glándulas Salivales / Calicreínas / Terapia Genética / Síndrome de Sjögren / Interleucina-17 / Modelos Animales de Enfermedad Tipo de estudio: Risk_factors_studies Límite: Animals Idioma: En Revista: Arthritis Res Ther Asunto de la revista: REUMATOLOGIA Año: 2015 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Glándulas Salivales / Calicreínas / Terapia Genética / Síndrome de Sjögren / Interleucina-17 / Modelos Animales de Enfermedad Tipo de estudio: Risk_factors_studies Límite: Animals Idioma: En Revista: Arthritis Res Ther Asunto de la revista: REUMATOLOGIA Año: 2015 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido