Corticoids synergize with IL-1 in the induction of LCN2

Summary Objective 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 glucocorticoi...

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Bibliographic Details
Published in:Osteoarthritis and cartilage 2017-07, Vol.25 (7), p.1172-1178
Main Authors: Conde, J, Lazzaro, V, Scotece, M, Abella, V, Villar, R, López, V, Gonzalez-Gay, M.Á, Pino, J, Gómez, R, Mera, A, Gualillo, O
Format: Article
Language:English
Subjects:
Adrenal Cortex Hormones - pharmacology
Animals
Anti-Inflammatory Agents - pharmacology
Cell Line
Chondrocytes
Dose-Response Relationship, Drug
Drug Synergism
Glucocorticoid
Interleukin-1alpha - pharmacology
Lipocalin-2
Lipocalin-2 - metabolism
Mice
Mineralcorticoid
Mineralocorticoids - pharmacokinetics
Rheumatology
Signal Transduction
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Summary:Summary Objective 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. Materials and methods 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. Results 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. Conclusions 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.
ISSN:1063-4584
1522-9653
DOI:10.1016/j.joca.2017.01.017