Purpose

The respiratory syncytial virus (RSV) is a common respiratory virus that causes acute lower respiratory tract infectious diseases, particularly in young children and older individuals. Activated leukocyte cell adhesion molecule (ALCAM) is a membrane glycoprotein expressed in various cell types, including epithelial cells, and is associated with inflammatory responses and various cancers. However, the precise role of ALCAM in RSV-induced airway inflammation remains unclear, and our study aimed to explore this gap in the literature.

Methods

C57BL/6 wild-type, ALCAM knockout mice and airway epithelial cells were infected with RSV and the expression of ALCAM and inflammatory cytokines were measured. We also conducted further experiments using Anti-ALCAM antibody and recombinant ALCAM in airway epithelial cells.

Results

The expression levels of ALCAM and inflammatory cytokines increased in both RSV-infected mice and airway epithelial cells. Interestingly, IL-33 expression was significantly reduced in ALCAM-knockdown cells compared to control cells following RSV infection. Anti-ALCAM antibody treatment also reduced IL-33 expression following RSV infection. Furthermore, the phosphorylation of ERK1/2, p38, and JNK was diminished in ALCAM-knockdown cells compared to control cells following RSV infection. Notably, in the control cells, inhibition of these pathways significantly decreased the expression of IL-33. In vivo study also confirmed a reduction in inflammation induced by RSV infection in ALCAM deficient mice compared to wild-type mice.

Conclusion

These findings demonstrate that ALCAM contributes to RSV-induced airway inflammation at least partly by influencing IL-33 expression through mitogen-activated protein kinase signaling pathways. These results suggest that targeting ALCAM could be a potential therapeutic strategy for alleviating IL-33-associated lung diseases.

中文翻译：

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激活的白细胞细胞粘附分子通过调节 MAPK 信号通路调节 RSV 诱导的气道炎症中 IL-33 的表达

目的

呼吸道合胞病毒（RSV）是一种常见的呼吸道病毒，可引起急性下呼吸道传染病，特别是在幼儿和老年人中。激活的白细胞细胞粘附分子 (ALCAM) 是一种在包括上皮细胞在内的多种细胞类型中表达的膜糖蛋白，与炎症反应和多种癌症相关。然而，ALCAM 在 RSV 诱导的气道炎症中的确切作用仍不清楚，我们的研究旨在探讨文献中的这一空白。

方法

用RSV感染C57BL/6野生型、ALCAM敲除小鼠和气道上皮细胞，并测量ALCAM和炎症细胞因子的表达。我们还在气道上皮细胞中使用抗 ALCAM 抗体和重组 ALCAM 进行了进一步的实验。

结果

RSV 感染小鼠和气道上皮细胞中 ALCAM 和炎症细胞因子的表达水平均增加。有趣的是，与 RSV 感染后的对照细胞相比，ALCAM 敲低细胞中的 IL-33 表达显着降低。抗 ALCAM 抗体治疗还降低了 RSV 感染后 IL-33 的表达。此外，与 RSV 感染后的对照细胞相比，ALCAM 敲低细胞中 ERK1/2、p38 和 JNK 的磷酸化减弱。值得注意的是，在对照细胞中，抑制这些途径会显着降低 IL-33 的表达。体内研究还证实，与野生型小鼠相比，ALCAM 缺陷小鼠由 RSV 感染引起的炎症减少。

结论

这些发现表明，ALCAM 至少部分通过丝裂原激活的蛋白激酶信号通路影响 IL-33 表达，从而导致 RSV 诱导的气道炎症。这些结果表明，靶向 ALCAM 可能是减轻 IL-33 相关肺部疾病的潜在治疗策略。