RRC ID 52092
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)