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

作者: Vanessa Abella , Morena Scotece , Javier Conde , Verónica López , Claudio Pirozzi

DOI: 10.1038/SREP20356

关键词:

摘要: Progranulin (PGRN) is a recently identified adipokine that 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 various damage-associated molecular patterns, leading inflammatory condition. So far, no data exist PGRN effects in conditions induced by IL1β or lipopolysaccharide (LPS). Here, we investigated the potential IL1β- LPS-induced responses chondrocytes. Human osteoarthritic chondrocytes and ATDC-5 cells were treated with presence not LPS. First, showed recombinant had on cell viability. We present evidence expression was increased during differentiation line. Moreover, mRNA protein cartilage, synovial infrapatellar fat pad tissue samples from OA patients. levels are upregulated under TNFα stimulation. Our able significantly counteract IL1β-induced NOS2, COX2, MMP13 VCAM-1. NOS2 also decreased PGRN. These mediated, at least part, through TNFR1. Taken together, our results suggest has clear function.

参考文章(41)
Miguel Otero, Rocío Lago, Francisca Lago, Juan Jesús Gomez Reino, Oreste Gualillo, Signalling pathway involved in nitric oxide synthase type II activation in chondrocytes: synergistic effect of leptin with interleukin-1 Arthritis Research & Therapy. ,vol. 7, pp. 1- 11 ,(2005) , 10.1186/AR1708
Lucie Andrés Cerezo, Markéta Kuklová, Hana Hulejová, Zdeňka Vernerová, Nikola Kaspříková, David Veigl, Karel Pavelka, Jiří Vencovský, Ladislav Šenolt, Progranulin Is Associated with Disease Activity in Patients with Rheumatoid Arthritis. Mediators of Inflammation. ,vol. 2015, pp. 740357- 740357 ,(2015) , 10.1155/2015/740357
Anna Santoro, Javier Conde, Morena Scotece, Vanessa Abella, Verónica López, Jesús Pino, Rodolfo Gómez, Juan Jesús Gómez-Reino, Oreste Gualillo, Choosing the right chondrocyte cell line: Focus on nitric oxide. Journal of Orthopaedic Research. ,vol. 33, pp. 1784- 1788 ,(2015) , 10.1002/JOR.22954
Rodolfo Gómez, Amanda Villalvilla, Raquel Largo, Oreste Gualillo, Gabriel Herrero-Beaumont, TLR4 signalling in osteoarthritis—finding targets for candidate DMOADs Nature Reviews Rheumatology. ,vol. 11, pp. 159- 170 ,(2015) , 10.1038/NRRHEUM.2014.209
Xiao-Hui Bai, Da-Wei Wang, Li Kong, Yan Zhang, Yi Luan, Tatsuya Kobayashi, Henry M. Kronenberg, Xiu-Ping Yu, Chuan-ju Liu, ADAMTS-7, a direct target of PTHrP, adversely regulates endochondral bone growth by associating with and inactivating GEP growth factor. Molecular and Cellular Biology. ,vol. 29, pp. 4201- 4219 ,(2009) , 10.1128/MCB.00056-09
Toshiya Matsubara, Ayako Mita, Kohtaro Minami, Tetsuya Hosooka, Sohei Kitazawa, Kenichi Takahashi, Yoshikazu Tamori, Norihide Yokoi, Makoto Watanabe, Ei-ichi Matsuo, Osamu Nishimura, Susumu Seino, PGRN is a Key Adipokine Mediating High Fat Diet-Induced Insulin Resistance and Obesity through IL-6 in Adipose Tissue Cell Metabolism. ,vol. 15, pp. 38- 50 ,(2012) , 10.1016/J.CMET.2011.12.002
Miguel Otero, Rocío Lago, Rodolfo Gómez, Francisca Lago, Juan Jesús Gomez-Reino, Oreste Gualillo, Phosphatidylinositol 3-kinase, MEK-1 and p38 mediate leptin/interferon-gamma synergistic NOS type II induction in chondrocytes. Life Sciences. ,vol. 81, pp. 1452- 1460 ,(2007) , 10.1016/J.LFS.2007.09.007
Ke Xu, Yan Zhang, Kirill Ilalov, Cathy S. Carlson, Jian Q. Feng, Paul E. Di Cesare, Chuan-ju Liu, Cartilage Oligomeric Matrix Protein Associates with Granulin-Epithelin Precursor (GEP) and Potentiates GEP-stimulated Chondrocyte Proliferation Journal of Biological Chemistry. ,vol. 282, pp. 11347- 11355 ,(2007) , 10.1074/JBC.M608744200
Pu Wang, Fei Zhu, ZiQiu Tong, Konstantinos Konstantopoulos, Response of chondrocytes to shear stress: antagonistic effects of the binding partners Toll-like receptor 4 and caveolin-1 The FASEB Journal. ,vol. 25, pp. 3401- 3415 ,(2011) , 10.1096/FJ.11-184861