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

Hatem A Elshabrawy; Michael V Volin; Abdul B Essani; Zhenlong L Chen; Iain B McInnes; Katrien Van Raemdonck; Karol Palasiewicz; Shiva Arami; Mark Gonzalez; Hossam M Ashour; Seung Jae Kim; Guo Fei Zhou; David A Fox; Shiva Shahrara

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

Hatem A Elshabrawy, Michael V Volin, Abdul B Essani, Zhenlong L Chen, Iain B McInnes, Katrien Van Raemdonck, Karol Palasiewicz, Shiva Arami, Mark Gonzalez, Hossam M Ashour, Seung Jae Kim, Guo Fei Zhou, David A Fox, Shiva Shahrara

University of South Florida

Research output: Contribution to journal › Article › peer-review

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-11R alpha 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-11R alpha was exclusively expressed in RA fibroblasts and endothelial cells, macrophages were not involved in IL-11 effector function. Ligation of IL-11 to IL-11R alpha 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-11R alpha can directly induce RA angiogenesis. In addition, secretion of proangiogenic factors from migrating fibroblasts potentiated by IL-11 can indirectly contribute to RA neovascularization.

Original language	American English
Journal	Default journal
State	Published - Jan 1 2018

Keywords

IL-11, RA synovial tissue, RA synovial fluid, Endothelial migration and tube formation, RA synovial tissue fibroblasts, bone marrow, disease, rheumatoid arthritis, human colorectal adenocarcinoma

Disciplines

Cardiovascular Diseases
Medical Sciences

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Elshabrawy, H. A., Volin, M. V., Essani, A. B., Chen, Z. L., McInnes, I. B., Van Raemdonck, K., Palasiewicz, K., Arami, S., Gonzalez, M., Ashour, H. M., Kim, S. J., Zhou, G. F., Fox, D. A., & Shahrara, S. (2018). IL-11 facilitates a novel connection between RA joint fibroblasts and endothelial cells. Default journal. https://login.ezproxy.lib.usf.edu/login?url=https://doi.org/10.1007/s10456-017-9589-y

Elshabrawy, HA, Volin, MV, Essani, AB, Chen, ZL, McInnes, IB, Van Raemdonck, K, Palasiewicz, K, Arami, S, Gonzalez, M, Ashour, HM, Kim, SJ, Zhou, GF, Fox, DA & Shahrara, S 2018, 'IL-11 facilitates a novel connection between RA joint fibroblasts and endothelial cells', Default journal. <https://login.ezproxy.lib.usf.edu/login?url=https://doi.org/10.1007/s10456-017-9589-y>

@article{2d32318736df4f01bc10e9844ec197ca,

title = "IL-11 facilitates a novel connection between RA joint fibroblasts and endothelial cells",

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-11R alpha 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-11R alpha was exclusively expressed in RA fibroblasts and endothelial cells, macrophages were not involved in IL-11 effector function. Ligation of IL-11 to IL-11R alpha 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-11R alpha can directly induce RA angiogenesis. In addition, secretion of proangiogenic factors from migrating fibroblasts potentiated by IL-11 can indirectly contribute to RA neovascularization.",

keywords = "IL-11, RA synovial tissue, RA synovial fluid, Endothelial migration and tube formation, RA synovial tissue fibroblasts, bone marrow, disease, rheumatoid arthritis, human colorectal adenocarcinoma",

author = "Elshabrawy, {Hatem A} and Volin, {Michael V} and Essani, {Abdul B} and Chen, {Zhenlong L} and McInnes, {Iain B} and {Van Raemdonck}, Katrien and Karol Palasiewicz and Shiva Arami and Mark Gonzalez and Ashour, {Hossam M} and Kim, {Seung Jae} and Zhou, {Guo Fei} and Fox, {David A} and Shiva Shahrara",

note = "Elshabrawy, H.A., Volin, M.V., Essani, A.B. et al. “IL-11 facilitates a novel connection between RA joint fibroblasts and endothelial cells.” Angiogenesis (2018) 21: 215-228. https://doi.org/10.1007/s10456-017-9589-y",

year = "2018",

month = jan,

day = "1",

language = "American English",

journal = "Default journal",

}

TY - JOUR

T1 - IL-11 facilitates a novel connection between RA joint fibroblasts and endothelial cells

AU - Elshabrawy, Hatem A

AU - Volin, Michael V

AU - Essani, Abdul B

AU - Chen, Zhenlong L

AU - McInnes, Iain B

AU - Van Raemdonck, Katrien

AU - Palasiewicz, Karol

AU - Arami, Shiva

AU - Gonzalez, Mark

AU - Ashour, Hossam M

AU - Kim, Seung Jae

AU - Zhou, Guo Fei

AU - Fox, David A

AU - Shahrara, Shiva

N1 - Elshabrawy, H.A., Volin, M.V., Essani, A.B. et al. “IL-11 facilitates a novel connection between RA joint fibroblasts and endothelial cells.” Angiogenesis (2018) 21: 215-228. https://doi.org/10.1007/s10456-017-9589-y

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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-11R alpha 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-11R alpha was exclusively expressed in RA fibroblasts and endothelial cells, macrophages were not involved in IL-11 effector function. Ligation of IL-11 to IL-11R alpha 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-11R alpha can directly induce RA angiogenesis. In addition, secretion of proangiogenic factors from migrating fibroblasts potentiated by IL-11 can indirectly contribute to RA neovascularization.

AB - 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-11R alpha 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-11R alpha was exclusively expressed in RA fibroblasts and endothelial cells, macrophages were not involved in IL-11 effector function. Ligation of IL-11 to IL-11R alpha 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-11R alpha can directly induce RA angiogenesis. In addition, secretion of proangiogenic factors from migrating fibroblasts potentiated by IL-11 can indirectly contribute to RA neovascularization.

KW - IL-11, RA synovial tissue, RA synovial fluid, Endothelial migration and tube formation, RA synovial tissue fibroblasts, bone marrow, disease, rheumatoid arthritis, human colorectal adenocarcinoma

UR - https://digitalcommons.usf.edu/fac_publications/3238

UR - https://login.ezproxy.lib.usf.edu/login?url=https://doi.org/10.1007/s10456-017-9589-y

M3 - Article

JO - Default journal

JF - Default journal

ER -

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

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