CC16 Regulates Inflammation, ROS Generation and Apoptosis in Bronchial Epithelial Cells during Klebsiella pneumoniae Infection.
CC16 Regulates Inflammation, ROS Generation and Apoptosis in Bronchial Epithelial Cells during Klebsiella pneumoniae Infection.
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DOI：
10.3390/ijms222111459
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发表时间：
2021-10-24
影响因子：
5.6
通讯作者：
Zhang D
中科院分区：
文献类型：
--
作者：
Almuntashiri S;Han Y;Zhu Y;Dutta S;Niazi S;Wang X;Siddiqui B;Zhang D
在美国，革兰氏阴性（G-）细菌是医院获得性肺炎的主要原因。G-细菌造成的毁灭性损害是由于杀菌作用的不平衡和压倒性的炎症。尽管经过了几十年的研究，失控性炎症发展的潜在机制仍然不完全清楚。Clara细胞蛋白16 （CC16）又称子宫红蛋白，是Clara细胞分泌的主要蛋白，也是支气管肺泡灌洗液（BALF）中含量最多的蛋白。然而，CC16在G-细菌感染中的调控和功能尚不清楚。在本研究中，我们旨在评估CC16在肺炎克雷伯菌（K. pneu）应答中的调控作用，并探讨CC16在支气管上皮细胞中的作用。肺炎克雷伯菌感染后，我们发现CC16 mRNA在支气管上皮细胞中的表达明显降低。我们的数据还显示，肺炎克雷伯菌感染上调了BEAS-2B细胞中的细胞因子和趋化因子基因，包括IL-1β、IL-6和IL-8。内源性过表达的CC16在BEAS-2B细胞中通过降低这些标记物发挥抗炎作用。我们还观察到内源性CC16可以抑制NF-κB报告基因的活性。相比之下，重组CC16 （rCC16）对肺炎克雷伯感染细胞没有抗炎作用，也没有抑制NF-κB启动子活性。此外，CC16的过表达降低了活性氧（ROS）水平，保护BEAS-2B细胞免受肺炎克雷伯菌诱导的凋亡。
Gram-negative (G-) bacteria are the leading cause of hospital-acquired pneumonia in the United States. The devastating damage caused by G- bacteria results from the imbalance of bactericidal effects and overwhelming inflammation. Despite decades of research, the underlying mechanisms by which runaway inflammation is developed remain incompletely understood. Clara Cell Protein 16 (CC16), also known as uteroglobin, is the major protein secreted by Clara cells and the most abundant protein in bronchoalveolar lavage fluid (BALF). However, the regulation and functions of CC16 during G- bacterial infection are unknown. In this study, we aimed to assess the regulation of CC16 in response to Klebsiella pneumoniae (K. pneu) and to investigate the role of CC16 in bronchial epithelial cells. After K. pneu infection, we found that CC16 mRNA expression was significantly decreased in bronchial epithelial cells. Our data also showed that K. pneu infection upregulated cytokine and chemokine genes, including IL-1β, IL-6, and IL-8 in BEAS-2B cells. Endogenously overexpressed CC16 in BEAS-2B cells provided an anti-inflammatory effect by reducing these markers. We also observed that endogenous CC16 can repress NF-κB reporter activity. In contrast, the recombinant CC16 (rCC16) did not show an anti-inflammatory effect in K. pneu-infected cells or suppression of NF-κB promoter activity. Moreover, the overexpression of CC16 reduced reactive oxygen species (ROS) levels and protected BEAS-2B cells from K. pneu-induced apoptosis.
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影响因子：
3.9
作者：
Almuntashiri S;Zhu Y;Han Y;Wang X;Somanath PR;Zhang D
通讯作者：
Zhang D
DOI：
10.3109/15412555.2014.948994
发表时间：
2015-08-01
影响因子：
2.2
作者：
Kokuho, Nariaki;Ishii, Takeo;Kida, Kozui
通讯作者：
Kida, Kozui
DOI：
10.1152/ajplung.00115.2016
发表时间：
2016-08-01
影响因子：
4.9
作者：
Kulkarni, Tejaswini;de Andrade, Joao;Thannickal, Victor J.
通讯作者：
Thannickal, Victor J.
DOI：
10.1164/ajrccm.161.1.9904073
发表时间：
2000-01-01
影响因子：
24.7
作者：
Laing, IA;Hermans, C;Le Souëf, PN
通讯作者：
Le Souëf, PN
影响因子：
5.6
作者：
Lin, Jinle;Li, Jiemei;Zeng, Xiaobin
通讯作者：
Zeng, Xiaobin