Inhibition of transglutaminase 2 enzymatic activity ameliorates the anti-angiogenic effects of coeliac disease autoantibodies

Sergio Caja, Essi Myrsky, Ilma R. Korponay-Szabo, Cristina Nadalutti, Ana-Marija Sulic, Miha Lavric, Daniele Sblattero, Roberto Marzari, Russell Collighan, Alexandre Mongeot, Martin Griffin, Markku Mäki, Katri Kaukinen, Katri Lindfors

Research output: Contribution to journalArticle

Abstract

Objective. Earlier work has demonstrated that serum autoantibodies from coeliac patients targeted against transglutaminase 2 (TG2) inhibit in vitro angiogenesis. The aim of this study was to establish whether coeliac patient-derived monoclonal TG2-targeted antibodies produced by recombination technology exert similar anti-angiogenic effects to serum-derived coeliac autoantibodies. In addition, we studied whether the monoclonal patient autoantibodies modulate endothelial cell TG2 activity and whether such modulation is related to the anti-angiogenic effects. Material and methods. The influence of coeliac patient-derived monoclonal TG2-targeted antibodies on endothelial cell tubule formation was studied using a three-dimensional angiogenic cell culture model. Endothelial cell TG2 enzymatic activity was determined by means of a live-cell enzyme-linked immunosorbent assay. Results. Coeliac patient-derived monoclonal TG2-targeted antibodies produced by recombination technology inhibited endothelial tubule formation and enhanced the crosslinking activity of TG2. When this enzymatic activity was inhibited using site-directed irreversible TG2 inhibitors in the presence of autoantibodies, in vitro angiogenesis reverted to the control level. Conclusions. Since we found a significant negative correlation between endothelial cell angiogenesis and TG2 activity, we suggest that the anti-angiogenic effects of coeliac patient-derived TG2-targeted autoantibodies are exerted by enhanced enzymatic activity of TG2.
Original languageEnglish
Pages (from-to)421-427
Number of pages7
JournalScandinavian Journal of Gastroenterology
Volume45
Issue number4
DOIs
Publication statusPublished - Apr 2010

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    Caja, S., Myrsky, E., Korponay-Szabo, I. R., Nadalutti, C., Sulic, A-M., Lavric, M., Sblattero, D., Marzari, R., Collighan, R., Mongeot, A., Griffin, M., Mäki, M., Kaukinen, K., & Lindfors, K. (2010). Inhibition of transglutaminase 2 enzymatic activity ameliorates the anti-angiogenic effects of coeliac disease autoantibodies. Scandinavian Journal of Gastroenterology, 45(4), 421-427. https://doi.org/10.3109/00365520903540822