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The novel adipokine progranulin counteracts IL-1 and TLR4-driven inflammatory response in human and murine chondrocytes via TNFR1

Abstract: Progranulin (PGRN) is a recently identified adipokine that is supposed to have anti-inflammatory actions. The proinflammatory cytokine interleukin-1? (IL1?) stimulates several mediators of cartilage degradation. Toll like receptor-4 (TLR4) can bind to various damage-associated molecular patterns, leading to inflammatory condition. So far, no data exist of PGRN effects in inflammatory conditions induced by IL1? or lipopolysaccharide (LPS). Here, we investigated the anti-inflammatory potential of PGRN in IL1?- or LPS-induced inflammatory responses of chondrocytes. Human osteoarthritic chondrocytes and ATDC-5 cells were treated with PGRN in presence or not of IL1? or LPS. First, we showed that recombinant PGRN had no effects on cell viability. We present evidence that PGRN expression was increased during the differentiation of ATDC-5 cell line. Moreover, PGRN mRNA and protein expression is increased in cartilage, synovial and infrapatellar fat pad tissue samples from OA patients. PGRN mRNA levels are upregulated under TNF? and IL1? stimulation. Our data showed that PGRN is able to significantly counteract the IL1?-induced expression of NOS2, COX2, MMP13 and VCAM-1. LPS-induced expression of NOS2 is also decreased by PGRN. These effects are mediated, at least in part, through TNFR1. Taken together, our results suggest that PGRN has a clear antiinflammatory function.

Otras publicaciones de la misma revista o congreso con autores/as de la Universidad de Cantabria

 Fuente: Scientific Reports 2016 | 6:20356

Editorial: Nature Publishing Group

 Año de publicación: 2016

Nº de páginas: 9

Tipo de publicación: Artículo de Revista

 DOI: 10.1038/srep20356

ISSN: 2045-2322

Autores/as

ABELLA, VANESSA

SCOTECE, MORENA

CONDE, JAVIER

LÓPEZ, VERÓNICA

PIROZZI, CLAUDIO

PINO, JESÚS

GÓMEZ, RODOLFO

LAGO, FRANCISCA