Abella Vanessa, Scotece Morena, Conde Javier, López Verónica, Pirozzi Claudio, Pino Jesús, Gómez Rodolfo, Lago Francisca, González-Gay Miguel Ángel, Gualillo Oreste
SERGAS (Servizo Galego de Saude) and IDIS (Instituto de Investigación Sanitaria de Santiago), Research Laboratory 9, The NEIRID Lab (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases), Santiago University Clinical Hospital, Santiago de Compostela, 15706, Spain.
Universidade da Coruña (UDC), Departamento de Bioloxía Celular e Molecular, Campus de A Coruña, A Coruña, 15071, Spain.
Sci Rep. 2016 Feb 8;6:20356. doi: 10.1038/srep20356.
Progranulin (PGRN) is a recently identified adipokine that is supposed to have anti-inflammatory actions. The proinflammatory cytokine interleukin-1β (IL1β) 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 IL1β or lipopolysaccharide (LPS). Here, we investigated the anti-inflammatory potential of PGRN in IL1β- or LPS-induced inflammatory responses of chondrocytes. Human osteoarthritic chondrocytes and ATDC-5 cells were treated with PGRN in presence or not of IL1β 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 TNFα and IL1β stimulation. Our data showed that PGRN is able to significantly counteract the IL1β-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 anti-inflammatory function.
颗粒蛋白前体(PGRN)是一种最近发现的脂肪因子,被认为具有抗炎作用。促炎细胞因子白细胞介素-1β(IL1β)可刺激多种软骨降解介质。Toll样受体4(TLR4)可与多种损伤相关分子模式结合,导致炎症状态。到目前为止,尚无关于PGRN在IL1β或脂多糖(LPS)诱导的炎症状态中作用的数据。在此,我们研究了PGRN在IL1β或LPS诱导的软骨细胞炎症反应中的抗炎潜力。在存在或不存在IL1β或LPS的情况下,用PGRN处理人骨关节炎软骨细胞和ATDC-5细胞。首先,我们表明重组PGRN对细胞活力没有影响。我们提供的证据表明,在ATDC-5细胞系分化过程中PGRN表达增加。此外,OA患者的软骨、滑膜和髌下脂肪垫组织样本中PGRN mRNA和蛋白表达增加。在TNFα和IL1β刺激下,PGRN mRNA水平上调。我们的数据表明,PGRN能够显著对抗IL1β诱导的NOS2、COX2、MMP13和VCAM-1的表达。PGRN也可降低LPS诱导的NOS2表达。这些作用至少部分是通过TNFR1介导的。综上所述,我们的结果表明PGRN具有明确的抗炎功能。