Open Access
Article
Three TNFR-binding domains of PGRN act independently in inhibition of TNF-alpha binding and activity
Qingyun Tian1,Yunpeng Zhao1,Jyoti Joshi Mundra1,Elena Gonzalez-Gugel1,Jinlong Jian1,Sardar M Z Uddin1,Chuanju Liu1
1
Department of Orthopaedic Surgery, New York University School of Medicine, 301 East 17th Street, New York, NY 10003
DOI: 10.2741/4274 Volume 19 Issue 7, pp.1176-1185
Published: 01 June 2014
Abstract

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.

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Qingyun Tian, Yunpeng Zhao, Jyoti Joshi Mundra, Elena Gonzalez-Gugel, Jinlong Jian, Sardar M Z Uddin, Chuanju Liu. Three TNFR-binding domains of PGRN act independently in inhibition of TNF-alpha binding and activity. Frontiers in Bioscience-Landmark. 2014. 19(7); 1176-1185.