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VIP Modulates IL-22R1 Expression and Prevents the Contribution of Rheumatoid Synovial Fibroblasts to IL-22-Mediated Joint Destruction

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Abstract

Rheumatoid arthritis (RA) and osteoarthritis are two rheumatic diseases whose progression is associated with a chronic synovitis. Fibroblast-like synoviocytes (FLS) have been shown to play a pivotal role in initiating and perpetuating inflammatory and destructive processes in the rheumatoid joint. Recently, the stimulating role of IL-22 has been reported on RA-FLS contribution to joint destruction by means of the increase of proliferation and matrix-metalloproteinase-1 (MMP-1) and alarmin S100A8/A9 production. Besides, mediators potentially present in inflamed joints have been shown to increase the expression of IL-22/IL-22R1 axis, amplifying the capacity of FLS to respond to IL-22 signalling. Since targeting cytokines that govern FLS activation would allow controlling their contribution to synovial inflammation, the present study was designed to analyze the potential immunoregulatory capacity of vasoactive intestinal peptide (VIP) to counterbalance IL-22 effects on FLS behavior. Our results showed that VIP is able to downregulate the augmented expression of IL-22 specific receptor in FLS subjected to a proinflammatory milieu. Moreover, this study revealed the ability of VIP to inhibit the IL-22 stimulatory effects on proliferation as well as on expression of both MMP-1 and alarmins in RA-FLS. The present findings reinforce the potential of this neuroimmunopeptide as a therapeutic agent in rheumatic diseases.

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Acknowledgements

This work was supported by Fondo de Investigación Sanitaria, Instituto de Salud Carlos III (PI11/00195, PI12/00758 and RD12/0009/0002, RIER), and SII10/BMD-2350 from Comunidad Autónoma de Madrid (CAM), by grants from ISCIII to MC.

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Authors and Affiliations

  1. Departamento de Biología Celular, Facultad de Biología, Universidad Complutense de Madrid, Madrid, Spain

    Mar Carrión, Yasmina Juarranz, Iria V. Seoane, Irene Gutiérrez-Cañas & Rosa P. Gomariz

  2. Departamento de Biología Celular, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain

    Carmen Martínez

  3. Servicio de Reumatología. Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria la Princesa, Madrid, Spain

    Isidoro González-Álvaro

  4. Servicio de Reumatología, Instituto de Investigación Hospital 12 de Octubre (I + 12), Madrid, Spain

    José Luis Pablos

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  1. Mar Carrión
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  2. Yasmina Juarranz
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  3. Iria V. Seoane
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  4. Carmen Martínez
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  7. Irene Gutiérrez-Cañas
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  8. Rosa P. Gomariz
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Correspondence to Rosa P. Gomariz.

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Carrión, M., Juarranz, Y., Seoane, I.V. et al. VIP Modulates IL-22R1 Expression and Prevents the Contribution of Rheumatoid Synovial Fibroblasts to IL-22-Mediated Joint Destruction. J Mol Neurosci 52, 10–17 (2014). https://doi.org/10.1007/s12031-013-0177-3

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