Club cell 10-kDa protein (CC10) inhibits cPLA2/COX2 pathway to alleviate RSV-induced airway inflammation and AHR.
Club cell 10-kDa protein (CC10) inhibits cPLA2/COX2 pathway to alleviate RSV-induced airway inflammation and AHR.
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Club cell 10-kDa蛋白(CC10)抑制cPLA2/COX2途径，减轻RSV诱导的呼吸道炎症和AHR。
DOI：
10.1016/j.intimp.2020.106327
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发表时间：
2020-03
影响因子：
5.6
通讯作者：
Guangyuan Yu;Shi Mo;Leiqiong Gao;X. Wen;Shenglin Chen;X. Long;Xiao-hong Xie;Yu Deng;L. Ren;N. Zang;Sisi Chen;E. Liu
中科院分区：
文献类型：
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作者：
Guangyuan Yu;Shi Mo;Leiqiong Gao;X. Wen;Shenglin Chen;X. Long;Xiao-hong Xie;Yu Deng;L. Ren;N. Zang;Sisi Chen;E. Liu
呼吸道合胞病毒（RSV）是引起婴儿急性下呼吸道感染（LRTI）的最常见病毒病原体。气道上皮细胞，包括Club细胞，是RSV感染的主要靶标。主要由Club细胞产生的“Club细胞10-kDa蛋白”（CC 10）具有与感染、损伤和过敏反应相关的抗炎和免疫调节特性。然而，其在RSV感染中的作用尚未完全了解。在临床上，我们发现，在鼻咽吸出物（NPA）的水平，RSV毛细支气管炎住院的婴儿，明显低于那些没有LRTI，也与疾病的严重程度呈负相关。BALB/c小鼠支气管肺泡灌洗液（BALF）中的CC 10水平在感染后第5天也下降。当在小鼠中施用重组CC 10时，RSV诱导的气道炎症和气道高反应性（AHR）减轻。同样，抑制胞浆磷脂酶A2（cPLA 2）或环氧化酶2（COX 2）（cPLA 2的下游信号分子），均可减轻RSV诱导的气道炎症和AHR。CC 10的施用降低了由感染引起的小鼠肺中cPLA 2的磷酸化和考克斯-2的蛋白水平，从而为先前的报道提供了分子机制，即CC 10部分地通过抑制cPLA 2的活性而发挥保护作用。我们的结论是，CC 10抑制cPLA 2/COX 2通路，以减轻RSV诱导的肺气道炎症和AHR。
Respiratory syncytial virus (RSV) is the most common viral pathogen causing acute lower respiratory tract infections (LRTI) in infants. Airway epithelial cells, including Club cells, are primary targets of RSV infection. The “Club cell 10-kDa protein” (CC10), produced mainly by Club cells, possesses anti-inflammatory and immunoregulatory properties that are relevant in infection, injury, and allergic reactions. However, its role in the RSV infection is not fully understood. In the clinic, we found that levels of CC10 in the nasopharyngeal aspirates (NPA) of infants, hospitalized with RSV bronchiolitis, were significantly lower than those without LRTI, and were also negatively correlated with the severity of the disease. In BALB/c mice, the CC10 levels in the bronchoalveolar lavage fluid (BALF) were also decreased at the 5th day after infection. When recombinant CC10 was administrated in the mice, RSV-induced airway inflammation and airway hyperresponsiveness (AHR) were alleviated. Similarly, inhibition of cytosolic phospholipase A2 (cPLA2) or cyclooxygenase 2 (COX2), which is a downstream signaling molecule for cPLA2, both alleviated RSV-induced airway inflammation and AHR. Administration of CC10 reduced the phosphorylation of cPLA2 and protein levels of COX-2 in mouse lungs, resulting from infection, thus providing a molecular mechanism for previous reports that CC10 plays a protective role, partly through inhibiting the activity of cPLA2. We conclude that CC10 inhibits the cPLA2/COX2 pathway to alleviate RSV-induced lung airway inflammation and AHR.