title: Corticoids synergize with IL-1 in the induction of LCN2.
abstract: Lipocalin-2 (LCN2) is an adipokine that was first identified in neutrophil granules. In the last years it was recognized as a factor that could impair chondrocyte phenotype, cartilage homeostasis as well as growth plate development. Both pro-inflammatory cytokines and glucocorticoids (GCs) modulate LCN2 expression. Actually, GCs were found to be LCN2 inducers, suggesting that part of the negative actions exerted by these anti-inflammatory drugs at cartilage level could be mediated by this adipokine. So, in this study we wanted to investigate whether corticoids were able to act in synergy with IL-1 in the induction of LCN2 and the signaling pathway involved in this process.
  
  
  
  For the realization of this work, ATDC5 mouse chondrogenic cell line was used. We determined the mRNA and protein expression of LCN2 by real-time reverse transcription-polymerase chain reaction (RT-qPCR) and western blot respectively, after GC or mineralcorticoid treatment. Different signaling pathways inhibitors were also used.
  
  
  
  GC and mineralcorticoid were able to induce the expression of LCN2 in ATDC5 cells. Interestingly, both corticoids synergized with IL-1 in the induction of LCN2. The effect of these corticoids on the expression of LCN2 occurred through GC or mineralcorticoid receptors and the kinases PI3K, ERK1/2 and JAK2.
  
  
  
  Prolonged use of corticoids may have detrimental effects on cartilage homeostasis. Based on our results, we conclude that corticoids could increase the negative actions exerted by IL-1 by increasing the expression of LCN2.
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 de Compostela, Spain. Electronic address: jcondearanda@gmail.com.
authors.forename: J
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 de Compostela, Spain.
authors.forename: V
authors.initials: V
authors.lastname: Lazzaro
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 de Compostela, Spain.
authors.forename: M
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 de Compostela, Spain.
authors.forename: V
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 de Compostela, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Villar
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 de Compostela, Spain.
authors.forename: V
authors.initials: V
authors.lastname: López
authors.affiliation: Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, Universidad de Cantabria and IDIVAL, Santander, Spain.
authors.forename: M Á
authors.initials: MÁ
authors.lastname: Gonzalez-Gay
authors.affiliation: SERGAS (Servizo Galego de Saude), Division of Orthopaedics Surgery and Traumatology, Santiago University Clinical Hospital, Santiago de Compostela, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Pino
authors.affiliation: Musculoskeletal Pathology Laboratory, Institute IDIS, Santiago University Clinical Hospital, Santiago de Compostela, 15706, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Gómez
authors.affiliation: SERGAS (Servizo Galego de Saude), Division of Rheumatology, Santiago University Clinical Hospital, Santiago de Compostela, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Mera
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 de Compostela, Spain. Electronic address: oreste.gualillo@sergas.es.
authors.forename: O
authors.initials: O
authors.lastname: Gualillo
mesh_terms: D000305:Adrenal Cortex Hormones / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D053582:Interleukin-1alpha / Q000494:pharmacology*; D000071068:Lipocalin-2 / Q000378:metabolism*; D051379:Mice; D008901:Mineralocorticoids / Q000493:pharmacokinetics*; D015398:Signal Transduction
chemical_list: D000305:Adrenal Cortex Hormones; D000893:Anti-Inflammatory Agents; D053582:Interleukin-1alpha; D000071068:Lipocalin-2; D008901:Mineralocorticoids; C071332:Lcn2 protein, mouse
keywords: Chondrocytes; Glucocorticoid; Lipocalin-2; Mineralcorticoid