Brain cytokine mRNAs in anorectic rats bearing prostate adenocarcinoma tumor cells
Brain cytokine mRNAs in anorectic rats bearing prostate adenocarcinoma tumor cells
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DOI：
10.1152/ajpregu.1998.275.2.r566
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发表时间：
1998-08-01
影响因子：
2.8
通讯作者：
Gayle, D
中科院分区：
文献类型：
--
作者：
Plata-Salamán, CR;Ilyin, SE;Gayle, D
癌症始终与厌食症相关。前列腺癌的 Lobund-Wistar 大鼠模型表现出与人类疾病的许多方面相似的临床表现（包括厌食症）。细胞因子被认为与癌症相关的厌食症有关。在这里，我们研究了携带前列腺腺癌肿瘤细胞的厌食 Lobund-Wistar 大鼠特定大脑区域中摄食调节细胞因子和神经肽的 mRNA 谱。通过灵敏且特异的 RNase 保护测定，对白细胞介素 (IL)-1 β 系统成分（配体、信号受体、受体辅助蛋白、受体拮抗剂）、肿瘤坏死因子-α、转化生长因子-β 1、糖蛋白 130（IL-6 受体信号转导器）、阿片黑皮素原（POMC，阿片肽前体）和神经肽 Y (NPY) mRNA 进行分析。对同一大脑区域样本的所有成分进行了分析。数据显示，荷瘤大鼠的早期厌食症与所检查的大脑区域（小脑、皮质和下丘脑）中 IL-1 β mRNA 的上调有关。皮质和下丘脑中IL-1受体拮抗剂（IL-1Ra）mRNA和IL-1受体I型mRNA水平也显着增加。所有其他细胞因子成分、POMC 或 NPY mRNA 水平在荷瘤大鼠和配对喂养（对照）大鼠之间没有显着差异。在荷瘤大鼠的脾脏中，IL-1β mRNA 和 IL-1Ra mRNA 也显着上调。这些数据表明：1) 大脑中 IL-1 β mRNA 的上调可能与荷瘤 Lobund-Wistar 大鼠表现出的厌食症有关，2) 癌症期间离散脑区域细胞因子成分的体内特征对于了解癌症相关神经表现的潜在分子机制是必要的。
Cancer is consistently associated with anorexia. The Lobund-Wistar rat model of prostate cancer exhibits clinical manifestations (including anorexia) that resemble many aspects of the human disease. Cytokines are proposed to be involved in cancer-associated anorexia. Here we investigated mRNA profiles of feeding-modulatory cytokines and neuropeptides in specific brain regions of anorectic Lobund-Wistar rats bearing prostate adenocarcinoma tumor cells. Interleukin (IL)-1 beta system components (ligand, signaling receptor, receptor accessory proteins, receptor antagonist), tumor necrosis factor-alpha, transforming growth factor-beta 1, glycoprotein 130 (IL-6 receptor signal transducer), proopiomelanocortin (POMC, opioid peptide precursor), and neuropeptide Y (NPY) mRNAs were analyzed with sensitive and specific RNase protection assays. The same brain region sample was assayed for all components. The data show that early anorexia in tumor-bearing rats was associated with an upregulation of IL-1 beta mRNA in the brain regions examined (cerebellum, cortex, and hypothalamus). IL-1 receptor antagonist (IL-1Ra) mRNA and IL-1 receptor type I mRNA levels were also significantly increased in the cortex and hypothalamus. All other cytokine components, POMC, or NPY mRNA levels were not significantly different between tumor-bearing and pair-fed (control) rats. IL-1 beta mRNA and IL-1Ra mRNA were also significantly upregulated in the spleen of tumor-bearing rats. These data suggest that 1) IL-1 beta mRNA upregulation in the brain may be relevant to the anorexia exhibited by the tumor-bearing Lobund-Wistar rat and 2) in vivo characterization of cytokine components in discrete brain regions during cancer is necessary to understand underlying molecular mechanisms responsible for cancer-associated neurological manifestations.