IL-11 facilitates a novel connection between RA joint fibroblasts and endothelial cells |
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| Authors: | Hatem A. Elshabrawy Michael V. Volin Abdul B. Essani Zhenlong Chen Iain B. McInnes Katrien Van Raemdonck Karol Palasiewicz Shiva Arami Mark Gonzalez Hossam M. Ashour Seung-jae Kim Guofei Zhou David A. Fox Shiva Shahrara |
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| Affiliation: | 1.Department of Pharmaceutical and Biomedical Sciences,California Northstate University College of Pharmacy,ELK Grove,USA;2.Jesse Brown VA Medical Center,Chicago,USA;3.Division of Rheumatology, Department of Medicine,University of Illinois at Chicago,Chicago,USA;4.Department of Microbiology and Immunology,Midwestern University,Downers Grove,USA;5.Institute of Infection, Immunity and Inflammation,University of Glasgow,Glasgow,UK;6.Department of Orthopaedic Surgery,University of Illinois at Chicago,Chicago,USA;7.Department of Biological Sciences, College of Arts and Sciences,University of South Florida St. Petersburg,St. Petersburg,USA;8.Department of Microbiology and Immunology, Faculty of Pharmacy,Cairo University,Cairo,Egypt;9.Department of Pediatrics,University of Illinois at Chicago,Chicago,USA;10.Division of Rheumatology and Clinical Autoimmunity Center of Excellence,University of Michigan,Ann Arbor,USA |
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| Abstract: | IL-11 has been detected in inflamed joints; however, its role in the pathogenesis of arthritis is not yet clear. Studies were conducted to characterize the expression and functional significance of IL-11 and IL-11Rα in rheumatoid arthritis (RA). IL-11 levels were elevated in RA synovial fluid (SF) compared to osteoarthritis (OA) SF and plasma from RA, OA and normal individuals (NLs). Morphologic studies established that IL-11 was detected in lining fibroblasts and macrophages in addition to sublining endothelial cells and macrophages at higher levels in RA compared to NL synovial tissues. Since IL-11Rα was exclusively expressed in RA fibroblasts and endothelial cells, macrophages were not involved in IL-11 effector function. Ligation of IL-11 to IL-11Rα strongly provoked fibroblast infiltration into RA joint, while cell proliferation was unaffected by this process. Secretion of IL-8 and VEGF from IL-11 activated RA fibroblasts was responsible for the indirect effect of IL-11 on endothelial cell transmigration and tube formation. Moreover, IL-11 blockade impaired RA SF capacity to elicit endothelial cell transmigration and tube formation. We conclude that IL-11 binding to endothelial IL-11Rα can directly induce RA angiogenesis. In addition, secretion of proangiogenic factors from migrating fibroblasts potentiated by IL-11 can indirectly contribute to RA neovascularization. |
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