Gastrin-releasing peptide (GRP) is an evolutionarily well-conserved neuropeptide that was originally recognized for its ability to mediate gastric acid secretion in the gut. More recently, however, GRP has been implicated in pulmonary lung inflammatory diseases including bronchopulmonary dysplasia, chronic obstructive pulmonary disease, emphysema, and others. Antagonizing GRP or its receptor mitigated lethality associated with the onset of viral pneumonia in a well-characterized mouse model of influenza. In mice treated therapeutically with the small-molecule GRP inhibitor, NSC77427, increased survival was accompanied by decreased numbers of GRP-producing pulmonary neuroendocrine cells, improved lung histopathology, and suppressed cytokine gene expression. In addition, in vitro studies in macrophages indicate that GRP synergizes with the prototype TLR4 agonist, lipopolysaccharide, to induce cytokine gene expression. Thus, these findings reveal that GRP is a previously unidentified mediator of influenza-induced inflammatory disease that is a potentially novel target for therapeutic intervention.

中文翻译：

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胃泌素释放肽介导的信号传导在宿主对流感感染的反应中的新作用。

胃泌素释放肽 (GRP) 是一种进化上非常保守的神经肽，最初因其在肠道中介导胃酸分泌的能力而得到认可。然而，最近，GRP 与肺部炎症性疾病有关，包括支气管肺发育不良、慢性阻塞性肺病、肺气肿等。在充分表征的流感小鼠模型中，拮抗 GRP 或其受体可减轻与病毒性肺炎发作相关的致死率。在用小分子 GRP 抑制剂 NSC77427 进行治疗的小鼠中，存活率的提高伴随着产生 GRP 的肺神经内分泌细胞数量的减少、肺组织病理学的改善和细胞因子基因表达的抑制。此外，巨噬细胞的体外研究表明，GRP 与原型 TLR4 激动剂脂多糖协同作用，以诱导细胞因子基因表达。因此，这些发现表明 GRP 是一种以前未被识别的流感引起的炎症性疾病的介质，它是治疗干预的潜在新靶点。