Potential roles of cytokines and chemokines in human intervertebral disc degeneration: interleukin-1 is a master regulator of catabolic processes

Potential roles of cytokines and chemokines in human intervertebral disc degeneration: interleukin-1 is a master regulator of catabolic processes
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DOI:
10.1016/j.joca.2015.02.017
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发表时间:
2015-07-01
影响因子:
7
通讯作者:
Le Maitre, C. L.
Le Maitre, C. L.
中科院分区:
医学2区
文献类型:
--
作者:
Phillips, K. L. E.;Cullen, K.;Le Maitre, C. L.

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目的:这些研究探讨了细胞因子和趋化因子受体在髓核(NP)细胞,和细胞外基质(ECM)成分的mRNA水平的受体刺激的影响,降解酶和细胞因子和趋化因子expression.Method:免疫组织化学(IHC)进行本地化表达的CD 4,CCR 1,CXCR 1和CXCR 2在人类NP组织样本。结果:免疫组化检测到NP细胞表达CD 4、CCR 1、CXCR 1和CXCR 2。在退化和浸润的IVD组织样本中观察到CD 4和CXCR 2的差异表达谱。用IL-16、CCL 2、CCL 3、CCL 7或CXCL 8体外刺激原代人NP培养物未鉴定出对与ECM重塑或其它细胞因子和趋化因子表达相关的参数的任何调节作用。相反,IL-1被认为是调节ECM重塑和表达的所有其他细胞因子和趋化因子investigated.Conclusion:这项研究表明,NP细胞表达的细胞因子和趋化因子受体的数量,从而可以响应自分泌或旁分泌的方式NP细胞产生的细胞因子和趋化因子,特别是在组织变性。然而,该研究未能证明对ECM基因和降解酶或其他细胞因子和趋化因子的任何研究靶点的调节作用,IL-1除外。这表明IL-1是IVD内的主要调节剂,并且可能对过多的其他细胞因子和趋化因子发挥调节潜力。(C)2015国际骨关节炎研究学会。由爱思唯尔有限公司出版。保留所有权利。
Objective: These studies investigated cytokine and chemokine receptor profiles in nucleus pulposus (NP) cells, and the effects of receptor stimulation on mRNA levels of extracellular matrix (ECM) components, degrading enzymes and cytokine and chemokine expression.Method: Immunohistochemistry (IHC) was performed to localise expression of CD4, CCR1, CXCR1 and CXCR2 in human NP tissue samples. Effects of cytokine and chemokine stimulation was performed to investigate effects related to ECM remodelling and modulation of cytokine and chemokine mRNA expression.Results: IHC identified CD4, CCR1, CXCR1 and CXCR2 expression by NP cells. Differential expression profiles were observed for CD4 and CXCR2 in tissue samples from degenerate and infiltrated IVDs. In vitro stimulations of primary human NP cultures with IL-16, CCL2, CCL3, CCL7 or CXCL8 did not identify any modulatory effects on parameters associated with ECM remodelling or expression of other cytokines and chemokines. Conversely, IL-1 was seen to modulate ECM remodelling and expression of all other cytokines and chemokines investigated.Conclusion: This study demonstrates for the first time that NP cells express a number of cytokine and chemokine receptors and thus could respond in an autocrine or paracrine manner to cytokines and chemokines produced by NP cells, particularly during tissue degeneration. However, this study failed to demonstrate regulatory effects on ECM genes and degradative enzymes or other cytokines and chemokines for any target investigated, with the exception of IL-1. This suggests that IL-1 is a master regulator within the IVD and may exert regulatory potential over a plethora of other cytokines and chemokines. (C) 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.