PT  - JOURNAL ARTICLE
AU  - Van Rijssel, Jos
AU  - Timmerman, Ilse
AU  - Van Alphen, Floris P. J.
AU  - Hoogenboezem, Mark
AU  - Korchynskyi, Olexandr
AU  - Geerts, Dirk
AU  - Geissler, Judy
AU  - Reedquist, Kris A.
AU  - Niessen, Hans W. M.
AU  - Van Buul, Jaap D.
TI  - The Rho-GEF Trio regulates a novel pro-inflammatory pathway through the transcription factor Ets2
AID  - 10.1242/bio.20134382
DP  - 2013 Jun 15
TA  - Biology Open
PG  - 569--579
VI  - 2
IP  - 6
4099  - http://bio.biologists.org/content/2/6/569.short
4100  - http://bio.biologists.org/content/2/6/569.full
SO  - Biology Open2013 Jun 15; 2
AB  - Inflammation is characterized by endothelium that highly expresses numerous adhesion molecules to trigger leukocyte extravasation. Central to this event is increased gene transcription. Small Rho-GTPases not only control the actin cytoskeleton, but are also implicated in gene regulation. However, in inflammation, it is not clear how this is regulated. Here, we show that the guanine-nucleotide exchange factor Trio expression is increased upon inflammatory stimuli in endothelium. Additionally, increased Trio expression was found in the vessel wall of rheumatoid arthritis patients. Trio silencing impaired VCAM-1 expression. Finally, we excluded that Trio-controlled VCAM-1 expression used the classical NFκB or MAP-kinase pathways, but rather acts on the transcriptional level by increasing phosphorylation and nuclear translocalization of Ets2. These data implicate Trio in regulating inflammation and provide novel targets for therapeutic purposes to treat inflammatory diseases such as rheumatoid arthritis.