Graduate Institute of Biomedical Sciences, Chang Gung University, Tao-Yuan, Taiwan.
Neuroscience. 2010 Feb 17;165(4):1191-202. doi: 10.1016/j.neuroscience.2009.12.003. Epub 2009 Dec 11.
Noradrenergic inputs from the brainstem are critical for the central stress response. It has been suggested that endogenous interleukin-1beta (IL-1beta) is involved in norepinephrine (NE)-induced release of corticotropin-releasing hormone (CRH) from the paraventricular nucleus of the hypothalamus (PVN). However, no IL-1 receptor on PVN CRH neurons has been identified. Therefore we hypothesized that the action of IL-1beta in the PVN requires downstream modulators that eventually lead to CRH release by PVN neurons. In the current study, we used organotypic cultures from neonatal rat PVN which display neuroendocrine characteristics suitable for in vitro studies. Pharmacological treatments with NE or IL-1beta elicited nitric oxide (NO) release from the PVN cultures, implying that local NO might be a candidate for modulating the action of IL-1beta. In addition, NE treatments significantly increased IL-1beta and CRH release. Treatment with IL-1beta or sodium nitroprusside also induced CRH release. Next, we also showed that either an IL-1 receptor antagonist or NOS inhibitor Nomega-nitro-L-arginine (L-NNA) attenuated the NE-induced CRH release. These results suggest that IL-1beta and NO are involved in NE-induced CRH release. Moreover, we found that application of L-NNA attenuated IL-1beta-induced CRH release, indicating that NO likely mediates this process. In summary, the current study demonstrates that IL-1beta plays a significant role in NE-induced CRH release, and that neuroendocrine response in the PVN may depend on local NO action.
来自脑干的去甲肾上腺素能输入对于中枢应激反应至关重要。有人提出内源性白细胞介素-1β（IL-1β）参与了去甲肾上腺素（NE）诱导下丘脑室旁核（PVN）促肾上腺皮质释放激素（CRH）的释放。然而，尚未在 PVN CRH 神经元上鉴定出 IL-1 受体。因此，我们假设 IL-1β在 PVN 中的作用需要下游调节剂，这些调节剂最终导致 PVN 神经元释放 CRH。在目前的研究中，我们使用来自新生大鼠 PVN 的器官型培养物进行研究，这些培养物显示出适合体外研究的神经内分泌特征。用 NE 或 IL-1β进行药理学处理会从 PVN 培养物中释放出一氧化氮（NO），这意味着局部 NO 可能是调节 IL-1β作用的候选物质。此外，NE 处理会显著增加 IL-1β和 CRH 的释放。IL-1β或亚硝基铁氰化钠（sodium nitroprusside）的处理也会诱导 CRH 的释放。接下来，我们还表明，IL-1 受体拮抗剂或一氧化氮合酶抑制剂 Nω-硝基-L-精氨酸（Nomega-nitro-L-arginine，L-NNA）均可减弱 NE 诱导的 CRH 释放。这些结果表明，IL-1β和 NO 参与了 NE 诱导的 CRH 释放。此外，我们发现应用 L-NNA 可减弱 IL-1β诱导的 CRH 释放，表明 NO 可能介导了这一过程。总之，本研究表明，IL-1β在 NE 诱导的 CRH 释放中起重要作用，而 PVN 的神经内分泌反应可能取决于局部 NO 作用。
