Tumor necrosis factor α and interleukin-1β stimulate the expression of cyclooxygenase II but do not alter prostaglandin E2 receptor mRNA levels in cultured dorsal root ganglia cells
Tumor necrosis factor α and interleukin-1β stimulate the expression of cyclooxygenase II but do not alter prostaglandin E2 receptor mRNA levels in cultured dorsal root ganglia cells
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DOI：
10.1016/j.pain.2004.09.031
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发表时间：
2005-01-01
期刊：
影响因子：
7.4
通讯作者：
Vasko, MR
中科院分区：
文献类型：
--
作者：
Fehrenbacher, JC;Burkey, TH;Vasko, MR
转归或坏死因子α(TNFpha)和白介素1β(IL-1β)是能够改变感觉神经元敏感性的前炎性细胞因子。由于IL-1β和肿瘤坏死因子α诱导的致敏作用被诱导酶环氧合酶-II(COX-2)的抑制所阻断。我们检测了这些细胞因子是否能增加培养的背根节(DRG)中COX-2的表达。用免疫印迹法检测，用IL-1β或TNFα处理细胞培养后，以时间和浓度依赖的方式增加了COX-2的免疫活性。用10 ng/mlIL-1β或50 ng/mlTNFpha预处理24小时后，COX-2的表达分别增加50倍和8倍。免疫组织化学证实在培养的神经细胞和非神经细胞中都存在COX-2样免疫反应。加入IL-1受体拮抗剂可阻断IL-1β诱导的COX-2表达，但不能改变肿瘤坏死因子α刺激的COX-2表达增加。提示肿瘤坏死因子α的作用机制并不局限于增加IL-Iβ的表达。基础和肿瘤坏死因子α诱导的COX-2表达不依赖于NGF的存在。IL-1β和肿瘤坏死因子α处理24小时后，前列腺素E-2(PGE(2))产量增加2~4倍。COX-2抑制剂NS-398可阻断该作用。将培养物暴露于前列腺素E(2)、IL-1β或肿瘤坏死因子α。作用24 h不改变PGE(2)受体(EP)的mRNA水平。这些结果表明，在培养的DRG细胞中，肿瘤坏死因子α和IL-1β诱导了COX-2的功能性表达，而不是EP受体的功能表达，提示细胞因子诱导的感觉神经元敏化继发于前列腺素的产生，而不是EP受体的改变。(C)2004年国际疼痛研究协会。爱思唯尔出版，版权所有。
Turn or necrosis factor alpha (TNFalpha) and interleukin 1beta (IL- 1beta) are pro-intlammatory cytokines capable of altering the sensitivity of sensory neurons. Because sensitization elicited by IL-1beta and TNFalpha is blocked by inhibition of the inducible enzyme, cyclooxygenase-II (COX-2). we examined whether these cytokines could increase COX-2 expression in dorsal root ganglion (DRG) cultures. Treatment of cell Cultures with either IL-1beta or TNFalpha increases immunoreactive COX-2, as measured by immunoblotting, in a time-and concentration-dependent manner. A 24-h pretreatment with 10 ng/ml IL- 1beta or 50 ng/ml TNFalpha augmented COX-2 expression 50- and 8-fold over basal levels, respectively. Immunohistochemistry established the presence of COX-2-like immunoreactivity in both neuronal and non-neuronal cells ill Culture. The addition of IL-1 receptor antagonist blocked the induction of COX-2 expression by IL- 1beta, but did riot alter TNFalpha-stimulated increases in COX-2. indicating that the mechanism of TNFalpha, is not limited to increasing the expression of IL- Ibeta. The basal and TNFalpha-induced expression of COX-2 was riot dependent oil the presence of NGF in the growth media. IL-1beta and TNFalpha treatment for 24 It enhanced prosta.-landin E-2 (PGE(2)) production 2-4-fold. which was blocked by pretreatment with the COX-2 inhibitor, NS-398. Exposing cultures to PGE(2), IL-1beta, or TNFalpha. for 24 h did not alter PGE(2) receptor (EP) mRNA levels. These results indicate that TNFalpha and IL-1beta, induce the functional expression of COX-2 but not EP receptors in DRG cells in culture and suggest that cytokine-induced sensitization of sensory neurons is secondary to prostaglandin production and not alterations in EP receptors. (C) 2004 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.