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

被引：51

作者：

Abella, Vanessa ^{[1
,2
,3
]}

Scotece, Morena ^{[1
,2
]}

Conde, Javier ^{[1
,2
]}

Lopez, Veronica ^{[1
,2
]}

Pirozzi, Claudio ^{[1
,2
]}

Pino, Jesus ^{[4
]}

Gomez, Rodolfo ^{[1
,2
]}

Lago, Francisca ^{[1
,5
]}

Angel Gonzalez-Gay, Miguel ^{[6
,7
]}

Gualillo, Oreste ^{[1
,2
]}

机构：

[1] Univ Santiago, Clin Hosp, SERGAS Serv Galego Saude, Santiago De Compostela 15706, Spain

[2] Univ Santiago, Clin Hosp, IDIS Inst Invest Sanitaria Santiago,Res Lab 9, NEIRID Lab Neuroendocrine Interact Rheumatol & In, Santiago De Compostela 15706, Spain

[3] Univ Coruna UDC, Dept Biol & Celular Mol, Campus A Coruna, La Coruna, Spain

[4] Univ Santiago, Clin Hosp, Div Orthopaed Surg & Traumatol, SERGAS Serv Galego Saude, Santiago De Compostela 15706, Spain

[5] Univ Santiago, Clin Hosp, IDIS Inst Invest Sanitaria Santiago, Cellular & Mol Cardiol Lab,Res Lab 7, Santiago De Compostela 15706, Spain

[6] Univ Santiago, Clin Hosp, Div Rheumatol, SERGAS Serv Galego Saude, Santiago De Compostela 15706, Spain

[7] Hosp Univ Marques Valdecilla, IDIVAL, Div Rheumatol, Santander, Cantabria, Spain

来源：

SCIENTIFIC REPORTS | 2016年 / 6卷

关键词：

GRANULIN-EPITHELIN PRECURSOR; GROWTH-FACTOR; ALPHA; DEGENERATION; MEDIATORS; CYTOKINES; ARTHRITIS; ADAMTS-7; BINDING; PGRN;

D O I：

10.1038/srep20356

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Progranulin (PGRN) is a recently identified adipokine that is supposed to have anti-inflammatory actions. The proinflammatory cytokine interleukin-1 beta (IL1 beta) 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 beta or lipopolysaccharide (LPS). Here, we investigated the anti-inflammatory potential of PGRN in IL1 beta- or LPS-induced inflammatory responses of chondrocytes. Human osteoarthritic chondrocytes and ATDC-5 cells were treated with PGRN in presence or not of IL1 beta 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 alpha and IL1 beta stimulation. Our data showed that PGRN is able to significantly counteract the IL1 beta-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.

引用

页数：9

共 42 条

[41]

Progranulin deficiency exaggerates, whereas progranulin-derived Atsttrin attenuates, severity of dermatitis in mice [J].