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

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)

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)

[img]
Preview
Text
156061.pdf - Accepted Version

542kB

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
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 > Institute of Infection Immunity and Inflammation
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

University Staff: Request a correction | Enlighten Editors: Update this record