Abstract
| Language | English |
|---|---|
| Pages | 421-427 |
| Number of pages | 7 |
| Journal | Scandinavian Journal of Gastroenterology |
| Volume | 45 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Apr 2010 |
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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 journal › Article
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.
UR - http://www.scopus.com/inward/record.url?scp=77949903860&partnerID=8YFLogxK
U2 - 10.3109/00365520903540822
DO - 10.3109/00365520903540822
M3 - Article
VL - 45
SP - 421
EP - 427
JO - Scandinavian Journal of Gastroenterology
T2 - Scandinavian Journal of Gastroenterology
JF - Scandinavian Journal of Gastroenterology
SN - 0036-5521
IS - 4
ER -