Angiogenesis

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

  • 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
Original Paper
  • 213 Downloads

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.

Keywords

IL-11 RA synovial tissue RA synovial fluid Endothelial migration and tube formation RA synovial tissue fibroblasts 

Notes

Acknowledgements

This work was supported in part by awards from Department of Veteran’s Affairs MERIT Award 1I01BX002286, the National Institutes of Health R43AG057312, AR056099 and AR065778, funding provided by Department of Defense PR093477. We would like to acknowledge Dr. Rhonda Kineman for critically reviewing the paper and granting us access to use her laboratory microscope.

Authors’ contribution

HAE, SS designed the research; HAE, MVV, ABE, ZC, SJK, KV, KP, SS performed the research; HAE, ZC, MVV, KV, MK, HMA, SJK, IBM, DAF, SS analyzed the data; SA, GZ: Provided reagents; all the authors contributed to writing the paper: Writing the paper.

Compliance with ethical standards

Conflict of interest

All the authors declare that they have no conflict of interest.

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Copyright information

© Springer Science+Business Media B.V., part of Springer Nature 2018

Authors and Affiliations

  • Hatem A. Elshabrawy
    • 1
    • 2
    • 3
  • Michael V. Volin
    • 4
  • Abdul B. Essani
    • 2
    • 3
  • Zhenlong Chen
    • 2
    • 3
  • Iain B. McInnes
    • 5
  • Katrien Van Raemdonck
    • 2
    • 3
  • Karol Palasiewicz
    • 2
    • 3
  • Shiva Arami
    • 2
    • 3
  • Mark Gonzalez
    • 6
  • Hossam M. Ashour
    • 7
    • 8
  • Seung-jae Kim
    • 2
    • 3
  • Guofei Zhou
    • 9
  • David A. Fox
    • 10
  • Shiva Shahrara
    • 2
    • 3
  1. 1.Department of Pharmaceutical and Biomedical SciencesCalifornia Northstate University College of PharmacyELK GroveUSA
  2. 2.Jesse Brown VA Medical CenterChicagoUSA
  3. 3.Division of Rheumatology, Department of MedicineUniversity of Illinois at ChicagoChicagoUSA
  4. 4.Department of Microbiology and ImmunologyMidwestern UniversityDowners GroveUSA
  5. 5.Institute of Infection, Immunity and InflammationUniversity of GlasgowGlasgowUK
  6. 6.Department of Orthopaedic SurgeryUniversity of Illinois at ChicagoChicagoUSA
  7. 7.Department of Biological Sciences, College of Arts and SciencesUniversity of South Florida St. PetersburgSt. PetersburgUSA
  8. 8.Department of Microbiology and Immunology, Faculty of PharmacyCairo UniversityCairoEgypt
  9. 9.Department of PediatricsUniversity of Illinois at ChicagoChicagoUSA
  10. 10.Division of Rheumatology and Clinical Autoimmunity Center of ExcellenceUniversity of MichiganAnn ArborUSA

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