title: IL-36α: a novel cytokine involved in the catabolic and inflammatory response in chondrocytes.
abstract: Recent studies confer to IL-36α pro-inflammatory properties. However, little is known about the expression and function of IL-36α in cartilage. This study sought to analyze the expression of IL-36α in healthy and OA cartilage. Next, we determined the effects of recombinant IL-36α on catabolism and inflammation in chondrocytes. For completeness, part of the signaling pathway elicited by IL-36α was also explored. IL-36α expression was evaluated by immunohistochemistry and RT-qPCR. Expression of MMP-13, NOS2 and COX-2 was also determined in OA articular chondrocytes treated with recombinant IL-36α. IκB-α and P-p38 was explored by western blot. We observed a low constitutive expression of IL-36α in healthy human chondrocytes. However, OA chondrocytes likely expressed more IL-36α than healthy chondrocytes. In addition, immune cells infiltrated into the joint and PBMCs express higher levels of IL-36α in comparison to chondrocytes. OA chondrocytes, treated with IL-36α, showed significant increase in the expression of MMP-13, NOS2 and COX-2. Finally, IL-36α stimulated cells showed NFκB and p38 MAPK activated pathways. IL-36α acts as a pro-inflammatory cytokine at cartilage level, by increasing the expression of markers of inflammation and cartilage catabolism. Like other members of IL-1 family, IL-36α acts through the activation of NFκB and p38 MAPK pathway.
authors.affiliation: SERGAS (Servizo Galego de Saude) and IDIS (Instituto de Investigación Sanitaria de Santiago), the NEIRID Lab (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases), Research Laboratory 9, Santiago University Clinical Hospital, Santiago deCompostela, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Conde
authors.affiliation: SERGAS (Servizo Galego de Saude) and IDIS (Instituto de Investigación Sanitaria de Santiago), the NEIRID Lab (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases), Research Laboratory 9, Santiago University Clinical Hospital, Santiago deCompostela, Spain.
authors.forename: Morena
authors.initials: M
authors.lastname: Scotece
authors.affiliation: SERGAS (Servizo Galego de Saude) and IDIS (Instituto de Investigación Sanitaria de Santiago), the NEIRID Lab (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases), Research Laboratory 9, Santiago University Clinical Hospital, Santiago deCompostela, Spain.|Department of Molecular and Cellular Biology, University of Coruña (UDC), A Coruña, Spain.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Abella
authors.affiliation: SERGAS (Servizo Galego de Saude) and IDIS (Instituto de Investigación Sanitaria de Santiago), the NEIRID Lab (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases), Research Laboratory 9, Santiago University Clinical Hospital, Santiago deCompostela, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Lois
authors.affiliation: SERGAS (Servizo Galego de Saude) and IDIS (Instituto de Investigación Sanitaria de Santiago), the NEIRID Lab (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases), Research Laboratory 9, Santiago University Clinical Hospital, Santiago deCompostela, Spain.
authors.forename: Verónica
authors.initials: V
authors.lastname: López
authors.affiliation: Department of Morphologic Sciences, Faculty of Medicine, University of Santiago de Compostela, Santiago deCompostela, Spain.
authors.forename: Tomás
authors.initials: T
authors.lastname: García-Caballero
authors.affiliation: SERGAS (Servizo Galego de Saude), Division of Orthopaedics Surgery and Traumatology, Santiago University Clinical Hospital, Santiago deCompostela, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Pino
authors.affiliation: University of Santiago de Compostela, Department of Medicine and SERGAS (Servizo Galego de Saude) and IDIS (Instituto de Investigación Sanitaria de Santiago), Division of Rheumatology, Santiago University Clinical Hospital, Santiago deCompostela, Spain.
authors.forename: Juan Jesús
authors.initials: JJ
authors.lastname: Gómez-Reino
authors.affiliation: SERGAS (Servizo Galego de Saude) and IDIS (Instituto de Investigación Sanitaria de Santiago), the NEIRID Lab (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases), Research Laboratory 9, Santiago University Clinical Hospital, Santiago deCompostela, Spain.
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Gómez
authors.affiliation: SERGAS (Servizo Galego de Saude) and IDIS (Instituto de Investigación Sanitaria de Santiago), cellular and molecular Cardiology Laboratory, Research Laboratory 7, Santiago University Clinical Hospital, Santiago deCompostela, Spain.
authors.forename: Francisca
authors.initials: F
authors.lastname: Lago
authors.affiliation: SERGAS (Servizo Galego de Saude) and IDIS (Instituto de Investigación Sanitaria de Santiago), the NEIRID Lab (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases), Research Laboratory 9, Santiago University Clinical Hospital, Santiago deCompostela, Spain.
authors.forename: Oreste
authors.initials: O
authors.lastname: Gualillo
mesh_terms: D015415:Biomarkers; D016022:Case-Control Studies; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000378:metabolism*; D007375:Interleukin-1 / Q000235:genetics* / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010003:Osteoarthritis / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D015415:Biomarkers; C508586:IL36A protein, human; D007375:Interleukin-1; D053583:Interleukin-1beta; D016328:NF-kappa B; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D048051:p38 Mitogen-Activated Protein Kinases; D053509:Matrix Metalloproteinase 13