The pathways for peripheral-to-central immune communication (P→C I-comm) following sterile lung injury (SLI) are unknown. SLI evokes systemic and central inflammation, which alters central respiratory control and viscerosensory transmission in the nucleus tractus solitarii (nTS). These functional changes coincide with increased interleukin-1 beta (IL-1β) in the area postrema, a sensory circumventricular organ that connects P→C I-comm to brainstem circuits that control homeostasis. We hypothesize that IL-1β and its downstream transcriptional target, cyclooxygenase-2 (COX-2), mediate P→C I-comm in the nTS. In a rodent model of SLI induced by intratracheal bleomycin (Bleo), the sigh frequency and duration of post-sigh apnea increased in Bleo- compared to saline- treated rats one week after injury. This SLI-dependent change in respiratory control occurred concurrently with augmented IL-1β and COX-2 immunoreactivity (IR) in the funiculus separans (FS), a barrier between the AP and the brainstem. At this barrier, increases in IL-1β and COX-2 IR were confined to processes that stained for glial fibrillary acidic protein (GFAP) and that projected basolaterally to the nTS. Further, FS radial-glia did not express TNF-α or IL-6 following SLI. To test our hypothesis, we blocked central COX-1/2 activity by intracerebroventricular (ICV) infusion of Indomethacin (Ind). Continuous ICV Ind treatment prevented Bleo-dependent increases in GFAP+ and IL-1β+ IR, and restored characteristics of sighs that reset the rhythm. These data indicate that changes in sighs following SLI depend partially on activation of a central COX-dependent P→C I-comm via radial-glia of the FS.

中文翻译：

---

博莱霉素诱导的成年大鼠无菌性肺损伤后末梢神经胶质屏障区域的外周到中枢免疫通讯

无菌性肺损伤 (SLI) 后外周到中枢免疫通讯 (P→C I-comm) 的途径尚不清楚。SLI 引起全身和中枢炎症，从而改变孤束核 (nTS) 中的中枢呼吸控制和内脏感觉传递。这些功能变化与后区白细胞介素 1 β (IL-1β) 的增加相吻合，后区是一种感觉心室周围器官，将 P→C I-comm 连接到控制体内平衡的脑干回路。我们假设 IL-1β 及其下游转录靶点 cyclooxygenase-2 (COX-2) 介导 nTS 中的 P→C I-comm。在气管内博来霉素 (Bleo) 诱导的 SLI 啮齿动物模型中，与损伤后一周用盐水处理的大鼠相比，Bleo 的叹气频率和叹气后呼吸暂停的持续时间增加。这种依赖于 SLI 的呼吸控制变化与分离索 (FS) 中增强的 IL-1β 和 COX-2 免疫反应性 (IR) 同时发生，这是 AP 和脑干之间的屏障。在这个屏障处，IL-1β 和 COX-2 IR 的增加仅限于对胶质纤维酸性蛋白 (GFAP) 进行染色的过程，并且投射到 nTS 的基底外侧。此外，FS 放射状胶质细胞在 SLI 后不表达 TNF-α 或 IL-6。为了验证我们的假设，我们通过脑室内 (ICV) 注射消炎痛 (Ind) 来阻断中枢 COX-1/2 活性。连续 ICV Ind 治疗可防止 GFAP+ 和 IL-1β+ IR 的 Bleo 依赖性增加，并恢复重置节律的叹息特征。