Journal
FRONTIERS IN BIOSCIENCE-LANDMARK
Volume 19, Issue -, Pages 1176-1185Publisher
IMR PRESS
DOI: 10.2741/4274
Keywords
PGRN; TNF-alpha; TNFR; Atsttrin; Inflammation; Inhibition; TNF; Activity
Categories
Funding
- NIH [R01AR062207, R01AR061484, R56AI100901]
- Rheumatology Research Foundation
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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-alphabinding 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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