title: 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-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.
authors: 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.
authors: Vanessa
authors: V
authors: Abella
authors: 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.
authors: Morena
authors: M
authors: Scotece
authors: 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.
authors: Javier
authors: J
authors: Conde
authors: 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.
authors: Verónica
authors: V
authors: López
authors: 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.
authors: Claudio
authors: C
authors: Pirozzi
authors: SERGAS (Servizo Galego de Saude), Division of Orthopaedics Surgery and Traumatology, Santiago University Clinical Hospital, Santiago de Compostela, 15706, Spain.
authors: Jesús
authors: J
authors: Pino
authors: 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.
authors: Rodolfo
authors: R
authors: Gómez
authors: SERGAS (Servizo Galego de Saude) and IDIS (Instituto de Investigación Sanitaria de Santiago), Research Laboratory 7, Cellular and Molecular Cardiology Laboratory, Santiago University Clinical Hospital, Santiago de Compostela, 15706, Spain.
authors: Francisca
authors: F
authors: Lago
authors: SERGAS (Servizo Galego de Saude), Division of Rheumatology, Santiago University Clinical Hospital, Santiago de Compostela, 15706, Spain.|Division of Rheumatology, Hospital Universitario Marqués de Valdecilla, IDIVAL, Santander, Cantabria, Spain.
authors: Miguel Ángel
authors: MÁ
authors: González-Gay
authors: 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.
authors: Oreste
authors: O
authors: Gualillo
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000633:toxicity; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D051379:Mice; D010003:Osteoarthritis / Q000378:metabolism / Q000473:pathology; D000077153:Progranulins; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000494:pharmacology; D013583:Synovial Membrane / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D000077153:Progranulins; D047888:Receptors, Tumor Necrosis Factor, Type I; D011994:Recombinant Proteins; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D051546:Cyclooxygenase 2; D053509:Matrix Metalloproteinase 13