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Angiogenesis
Published in: Angiogenesis 2/2018

01-05-2018 | Original Paper

IL-11 facilitates a novel connection between RA joint fibroblasts and endothelial cells

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

Published in: Angiogenesis | Issue 2/2018

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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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Metadata
Title
IL-11 facilitates a novel connection between RA joint fibroblasts and endothelial cells
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
Publication date
01-05-2018
Publisher
Springer Netherlands
Published in
Angiogenesis / Issue 2/2018
Print ISSN: 0969-6970
Electronic ISSN: 1573-7209
DOI
https://doi.org/10.1007/s10456-017-9589-y

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