IMR Press / FBL / Volume 19 / Issue 7 / DOI: 10.2741/4274

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article
Three TNFR-binding domains of PGRN act independently in inhibition of TNF-alpha binding and activity
Show Less
1 Department of Orthopaedic Surgery, New York University Medical Center, New York, NY, 10003
2 Department of Cell Biology, New York University School of Medicine, New York, NY 10016
Academic Editor:Chuan-ju Liu
Front. Biosci. (Landmark Ed) 2014, 19(7), 1176–1185;
Published: 1 June 2014

PGRN was previously reported to bind to TNF receptors (TNFR) and is therapeutic against inflammatory arthritis. Here we present further evidences demonstrating the PGRN inhibition of TNF-alpha binding and activity, and clarifying the distinct mechanisms underlying TNF-alpha inhibition between PGRN and classic TNF-alpha-binding inhibitors. In addition, we present evidences indicating that three TNFR binding domains of PGRN act independently in binding to TNFR. Furthermore, changing the order of three TNFR-binding domains in Atsttrin, a PGRN-derived molecule composed of these TNFR-binding domains, does not affect its anti-inflammatory and anti-TNF activities in both collagen-induced inflammatory arthritis and human TNF-alpha transgenic mouse model. Taken together, these findings provide the additional molecular basis underlying PGRN/TNFR interaction and PGRN-mediated anti-inflammatory activity in various inflammatory diseases and conditions.

Back to top