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Soluble CD13 induces inflammatory arthritis by activating the bradykinin receptor B1.
Tsou, Pei-Suen; Lu, Chenyang; Gurrea-Rubio, Mikel; Muraoka, Sei; Campbell, Phillip L; Wu, Qi; Model, Ellen N; Lind, Matthew E; Vichaikul, Sirapa; Mattichak, Megan N; Brodie, William D; Hervoso, Jonatan L; Ory, Sarah; Amarista, Camila I; Pervez, Rida; Junginger, Lucas; Ali, Mustafa; Hodish, Gal; O'Mara, Morgan M; Ruth, Jeffrey H; Robida, Aaron M; Alt, Andrew J; Zhang, Chengxin; Urquhart, Andrew G; Lawton, Jeffrey N; Chung, Kevin C; Maerz, Tristan; Saunders, Thomas L; Groppi, Vincent E; Fox, David A; Amin, M Asif.
Afiliación
  • Tsou PS; Division of Rheumatology and Clinical Autoimmunity Center of Excellence, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
  • Lu C; Division of Rheumatology and Clinical Autoimmunity Center of Excellence, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
  • Gurrea-Rubio M; Department of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
  • Muraoka S; Division of Rheumatology and Clinical Autoimmunity Center of Excellence, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
  • Campbell PL; Division of Rheumatology and Clinical Autoimmunity Center of Excellence, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
  • Wu Q; Division of Rheumatology and Clinical Autoimmunity Center of Excellence, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
  • Model EN; Division of Rheumatology and Clinical Autoimmunity Center of Excellence, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
  • Lind ME; Division of Rheumatology and Clinical Autoimmunity Center of Excellence, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
  • Vichaikul S; Division of Rheumatology and Clinical Autoimmunity Center of Excellence, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
  • Mattichak MN; Division of Rheumatology and Clinical Autoimmunity Center of Excellence, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
  • Brodie WD; Division of Rheumatology and Clinical Autoimmunity Center of Excellence, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
  • Hervoso JL; Division of Rheumatology and Clinical Autoimmunity Center of Excellence, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
  • Ory S; Division of Rheumatology and Clinical Autoimmunity Center of Excellence, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
  • Amarista CI; Division of Rheumatology and Clinical Autoimmunity Center of Excellence, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
  • Pervez R; Division of Rheumatology and Clinical Autoimmunity Center of Excellence, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
  • Junginger L; Department of Orthopedic Surgery, University of Michigan Health System, Ann Arbor, Michigan, USA.
  • Ali M; Department of Orthopedic Surgery, University of Michigan Health System, Ann Arbor, Michigan, USA.
  • Hodish G; Division of Rheumatology and Clinical Autoimmunity Center of Excellence, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
  • O'Mara MM; Division of Rheumatology and Clinical Autoimmunity Center of Excellence, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
  • Ruth JH; Division of Rheumatology and Clinical Autoimmunity Center of Excellence, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
  • Robida AM; Division of Rheumatology and Clinical Autoimmunity Center of Excellence, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
  • Alt AJ; Pharmacology Department.
  • Zhang C; Pharmacology Department.
  • Urquhart AG; Department of Computational Medicine and Bioinformatics.
  • Lawton JN; Department of Orthopedic Surgery, University of Michigan Health System, Ann Arbor, Michigan, USA.
  • Chung KC; Department of Orthopedic Surgery, University of Michigan Health System, Ann Arbor, Michigan, USA.
  • Maerz T; Department of Orthopedic Surgery, University of Michigan Health System, Ann Arbor, Michigan, USA.
  • Saunders TL; Department of Orthopedic Surgery, University of Michigan Health System, Ann Arbor, Michigan, USA.
  • Groppi VE; Division of Rheumatology and Clinical Autoimmunity Center of Excellence, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
  • Fox DA; Biomedical Research Core Facilities, Transgenic Animal Model Core, and.
  • Amin MA; Center for Discovery of New Medicine, University of Michigan, Ann Arbor, Michigan, USA.
J Clin Invest ; 132(11)2022 06 01.
Article en En | MEDLINE | ID: mdl-35439173
CD13, an ectoenzyme on myeloid and stromal cells, also circulates as a shed, soluble protein (sCD13) with powerful chemoattractant, angiogenic, and arthritogenic properties, which require engagement of a G protein-coupled receptor (GPCR). Here we identify the GPCR that mediates sCD13 arthritogenic actions as the bradykinin receptor B1 (B1R). Immunofluorescence and immunoblotting verified high expression of B1R in rheumatoid arthritis (RA) synovial tissue and fibroblast-like synoviocytes (FLSs), and demonstrated binding of sCD13 to B1R. Chemotaxis, and phosphorylation of Erk1/2, induced by sCD13, were inhibited by B1R antagonists. In ex vivo RA synovial tissue organ cultures, a B1R antagonist reduced secretion of inflammatory cytokines. Several mouse arthritis models, including serum transfer, antigen-induced, and local innate immune stimulation arthritis models, were attenuated in Cd13-/- and B1R-/- mice and were alleviated by B1R antagonism. These results establish a CD13/B1R axis in the pathogenesis of inflammatory arthritis and identify B1R as a compelling therapeutic target in RA and potentially other inflammatory diseases.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Artritis Reumatoide / Antígenos CD13 / Sinoviocitos Límite: Animals Idioma: En Revista: J Clin Invest Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Artritis Reumatoide / Antígenos CD13 / Sinoviocitos Límite: Animals Idioma: En Revista: J Clin Invest Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos