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.
LanguageEnglish
Pages421-427
Number of pages7
JournalScandinavian Journal of Gastroenterology
Volume45
Issue number4
DOIs
Publication statusPublished - Apr 2010

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Celiac Disease
Autoantibodies
Abdomen
Endothelial Cells
Genetic Recombination
Antibodies
transglutaminase 2
Technology
Serum
Cell Culture Techniques
Enzyme-Linked Immunosorbent Assay

Cite this

Caja, Sergio ; Myrsky, Essi ; Korponay-Szabo, Ilma R. ; Nadalutti, Cristina ; Sulic, Ana-Marija ; Lavric, Miha ; Sblattero, Daniele ; Marzari, Roberto ; Collighan, Russell ; Mongeot, Alexandre ; Griffin, Martin ; Mäki, Markku ; Kaukinen, Katri ; Lindfors, Katri. / Inhibition of transglutaminase 2 enzymatic activity ameliorates the anti-angiogenic effects of coeliac disease autoantibodies. In: Scandinavian Journal of Gastroenterology. 2010 ; Vol. 45, No. 4. pp. 421-427.
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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.",
author = "Sergio Caja and Essi Myrsky and Korponay-Szabo, {Ilma R.} and Cristina Nadalutti and Ana-Marija Sulic and Miha Lavric and Daniele Sblattero and Roberto Marzari and Russell Collighan and Alexandre Mongeot and Martin Griffin and Markku M{\"a}ki and Katri Kaukinen and Katri Lindfors",
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Caja, S, Myrsky, E, Korponay-Szabo, IR, 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, vol. 45, no. 4, pp. 421-427. https://doi.org/10.3109/00365520903540822

Inhibition of transglutaminase 2 enzymatic activity ameliorates the anti-angiogenic effects of coeliac disease autoantibodies. / Caja, Sergio; Myrsky, Essi; Korponay-Szabo, Ilma R.; Nadalutti, Cristina; Sulic, Ana-Marija; Lavric, Miha; Sblattero, Daniele; Marzari, Roberto; Collighan, Russell; Mongeot, Alexandre; Griffin, Martin; Mäki, Markku; Kaukinen, Katri; Lindfors, Katri.

In: Scandinavian Journal of Gastroenterology, Vol. 45, No. 4, 04.2010, p. 421-427.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Inhibition of transglutaminase 2 enzymatic activity ameliorates the anti-angiogenic effects of coeliac disease autoantibodies

AU - Caja, Sergio

AU - Myrsky, Essi

AU - Korponay-Szabo, Ilma R.

AU - Nadalutti, Cristina

AU - Sulic, Ana-Marija

AU - Lavric, Miha

AU - Sblattero, Daniele

AU - Marzari, Roberto

AU - Collighan, Russell

AU - Mongeot, Alexandre

AU - Griffin, Martin

AU - Mäki, Markku

AU - Kaukinen, Katri

AU - Lindfors, Katri

PY - 2010/4

Y1 - 2010/4

N2 - 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.

AB - 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.

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