Effects of IL-1β, IL-6 or LIF on rat sensory neurons co-cultured with fibroblast-like cells

Effects of IL-1β, IL-6 or LIF on rat sensory neurons co-cultured with fibroblast-like cells
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DOI:
10.1002/jnr.10092
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发表时间:
2002-01-15
影响因子:
4.2
通讯作者:
Jerregård, H
Jerregård, H
中科院分区:
医学3区
文献类型:
--
作者:
Edoff, K;Jerregård, H

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炎症可能影响原位感觉神经纤维的局部存在,炎症介质影响体外感觉神经元。在本研究中,我们研究了白细胞介素-1 β (il -1 β)、白细胞介素-6 (IL-6)和白血病抑制因子(LIF)对新生大鼠感觉神经元与新生大鼠皮肤(sFLCs)或软骨膜(pFLCs)制备的成纤维细胞样细胞共培养的存活和神经突生长的影响。结果表明,两种FLC类型均表达所有三种细胞因子的受体。5 ng/ml细胞因子均可支持与sFLCs共培养的DRG神经元的存活。添加或不添加IL-6的可溶性IL-6受体(rsIL-6R)也能提高神经元的存活率。在与pFLCs共培养的细胞中,IL-6促进了神经元的存活,并随着细胞因子浓度的增加而增加。添加不含IL-6的rsIL-6R也能刺激神经元存活。0.5 ng/ml LIF刺激DRG神经元与sFLCs共培养的神经突生长,5 ng/ml LIF不影响其生长,50 ng/ml LIF抑制其生长。考虑到DRG神经元与pFLCs共培养,三种细胞因子中的任何一种50 ng/ml,以及rsIL-6R条件培养基,刺激了神经突起的生长。应用抗神经生长因子(NGF)抗体可降低观察到的一些细胞因子效应。我们的结论是,所检测的细胞因子在存活或神经新生方面影响DRG神经元,这种影响受细胞因子浓度和FLCs来源的影响,其中一些影响是间接的,可能是由FLCs释放的因子介导的。(C) 2002 Wiley-Liss, Inc。
Inflammation may affect the local presence of sensory nerve fibers in situ and inflammatory mediators influence sensory neurons in vitro. In the present study we have investigated effects of the cytokines interleukin-1beta (IL-1beta), interleukin-6 (IL-6), and leukemia inhibitory factor (LIF) on survival of and neurite growth from neonatal rat sensory neurons co-cultured with fibroblast-like cells prepared from neonatal rat skin (sFLCs) or perichondrium (pFLCs). The results showed that both FLC types expressed receptors for all three cytokines. Five ng/ml of either cytokine, but not lower or higher concentrations, supported survival of DRG neurons co-cultured with sFLCs. Neuronal survival was also enhanced by addition of the soluble IL-6 receptor (rsIL-6R) with or without IL-6. In co-cultures with pFLCs neuronal survival was promoted by IL-6, increasing with cytokine concentration. Addition of rsIL-6R without IL-6 did also stimulate neuronal survival. The growth of neurites from DRG neurons co-cultured with sFLCs was stimulated by 0.5 ng/ml LIF, unaffected by 5 ng/ml LIF and inhibited by 50 ng/ml LIF. Considering DRG neurons co-cultured with pFLCs, 50 ng/ml of either of the three cytokines, as well as rsIL-6R conditioned medium, stimulated neurite outgrowth. Some of the cytokine effects observed were reduced by application of antibodies against nerve growth factor (NGF). We conclude that that the cytokines examined affect DRG neurons in terms of survival or neuritogenesis, that the effects are influenced by cytokine concentration and the origin of the FLCs and that some of the effects are indirect, probably being mediated by factors released from FLCs. (C) 2002 Wiley-Liss, Inc.