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.