1. IL-11 facilitates a novel connection between RA joint fibroblasts and endothelial cells.
- Author
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Elshabrawy HA, Volin MV, Essani AB, Chen Z, McInnes IB, Van Raemdonck K, Palasiewicz K, Arami S, Gonzalez M, Ashour HM, Kim SJ, Zhou G, Fox DA, and Shahrara S
- Subjects
- Arthritis, Rheumatoid pathology, Endothelial Cells pathology, Female, Fibroblasts pathology, Humans, Interleukin-11 Receptor alpha Subunit metabolism, Interleukin-8 metabolism, Joints pathology, Male, Neovascularization, Pathologic pathology, Transendothelial and Transepithelial Migration, Vascular Endothelial Growth Factor A metabolism, Arthritis, Rheumatoid metabolism, Endothelial Cells metabolism, Fibroblasts metabolism, Interleukin-11 metabolism, Joints metabolism, Neovascularization, Pathologic metabolism
- 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.
- Published
- 2018
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