Elshabrawy, H. A. et al. (2018) IL-11 facilitates a novel connection between RA joint fibroblasts and endothelial cells. Angiogenesis, 21(2), pp. 215-228. (doi: 10.1007/s10456-017-9589-y) (PMID:29327326)
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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.
Item Type: | Articles |
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Keywords: | Endothelial migration and tube formation, IL-11, RA synovial fluid, RA synovial tissue, RA synovial tissue fibroblasts. |
Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | McInnes, Professor Iain |
Authors: | Elshabrawy, H. A., Volin, M. V., Essani, A. B., Chen, Z., McInnes, I. B., Van Raemdonck, K., Palasiewicz, K., Arami, S., Gonzalez, M., Ashour, H. M., Kim, S.-J., Zhou, G., Fox, D. A., and Shahrara, S. |
College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
Journal Name: | Angiogenesis |
Publisher: | Springer |
ISSN: | 0969-6970 |
ISSN (Online): | 1573-7209 |
Published Online: | 11 January 2018 |
Copyright Holders: | Copyright © 2018 Springer Science+Business Media B.V., part of Springer Nature |
First Published: | First published in Angiogenesis 21(2): 215-228 |
Publisher Policy: | Reproduced in accordance with the publisher copyright policy |
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