Email updates

Keep up to date with the latest news and content from JTM and BioMed Central.

This article is part of the supplement: 6th European Workshop on Immune-Mediated Inflammatory Diseases

Open Access Poster presentation

Non-canonical NF-κB signaling in endothelial cells may enhance synovial inflammation by stimulating angiogenesis

Ae-Ri Noort, Katinka PM van Zoest, Paul Peter Tak and Sander W Tas*

  • * Corresponding author: Sander W Tas

Author Affiliations

Division of Clinical Immunology & Rheumatology, Academic Medical Center, University of Amsterdam, The Netherlands

For all author emails, please log on.

Journal of Translational Medicine 2011, 9(Suppl 2):P50  doi:10.1186/1479-5876-9-S2-P50

The electronic version of this article is the complete one and can be found online at: http://www.translational-medicine.com/content/9/S2/P50


Published:23 November 2011

© 2011 Noort et al; licensee BioMed Central Ltd.

This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Background

Pathological angiogenesis can be observed in rheumatoid arthritis (RA) synovial tissue (ST) already in the earliest phase of disease and may be critical in the switch from acute to chronic inflammation. The chemokine CXCL12 is regulated by non-canonical NF-κB signaling and stimulates angiogenesis in endothelial cells (EC). Therefore, the non-canonical NF-κB pathway, with its key mediator NF-κB inducing kinase (NIK), may play an important role in pathological angiogenesis leading to the perpetuation of synovial inflammation in RA.

Objective

To study the role of non-canonical NF-κB signaling in pathological angiogenesis in RA.

Materials and methods

ST was obtained via mini-arthroscopy from inflamed joints of RA patients. Expression of NIK and CXCL12 was evaluated using immunohistochemistry and immunofluorescence (IF) microscopy. NIK expression was also studied in Grawitz tumor and breast cancer tissues. Next, the effects of non-canonical NF-κB signaling in EC were studied in vitro using angiogenesis/tube formation assays.

Results

NIK was highly expressed in vascular structures in RA ST. IF microscopy demonstrated that NIK and CXCL12 were both expressed in high endothelial venules and in EC of small (newly formed) blood vessels. In addition, NIK was also expressed in EC in Grawitz tumor and breast cancer tissues, whereas normal skin EC did not exhibit increased NIK expression. In vitro, EC treated with stimuli that induce non-canonical NF-κB signaling significantly enhanced tube formation 2,5-fold (p<0.05), which could be completely blocked by siRNA targeting NIK.

Conclusion

NIK is preferentially expressed in EC both in inflamed RA ST and in tumor tissues. In vitro, induction of non-canonical NF-κB signaling resulted in EC activation and enhanced angiogenesis, whereas selective blockade of this pathway using siRNA abrogated these effects. These findings point towards an important role of the non-canonical NF-κB pathway in (pathological) angiogenesis. This could be exploited for the development of new therapies not only for RA, but also for other diseases.