論文 - 詳細
RRC ID | 52092 |
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著者 | Conde J, Lazzaro V, Scotece M, Abella V, Villar R, López V, Gonzalez-Gay MÁ, Pino J, Gómez R, Mera A, Gualillo O. |
タイトル | Corticoids synergize with IL-1 in the induction of LCN2. |
ジャーナル | Osteoarthritis Cartilage |
Abstract |
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. |
巻・号 | 25(7) |
ページ | 1172-1178 |
公開日 | 2017-7-1 |
DOI | 10.1016/j.joca.2017.01.017 |
PII | S1063-4584(17)30049-3 |
PMID | 28185846 |
MeSH | Adrenal Cortex Hormones / pharmacology* Animals Anti-Inflammatory Agents / pharmacology* Cell Line Dose-Response Relationship, Drug Drug Synergism Interleukin-1alpha / pharmacology* Lipocalin-2 / metabolism* Mice Mineralocorticoids / pharmacokinetics* Signal Transduction |
IF | 4.793 |
引用数 | 8 |
リソース情報 | |
ヒト・動物細胞 | ATDC5(RCB0565) |