Cargando…

CC16 Regulates Inflammation, ROS Generation and Apoptosis in Bronchial Epithelial Cells during Klebsiella pneumoniae Infection

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 runawa...

Descripción completa

Detalles Bibliográficos
Autores principales: Almuntashiri, Sultan, Han, Yohan, Zhu, Yin, Dutta, Saugata, Niazi, Sara, Wang, Xiaoyun, Siddiqui, Budder, Zhang, Duo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8583934/
https://www.ncbi.nlm.nih.gov/pubmed/34768890
http://dx.doi.org/10.3390/ijms222111459
_version_ 1784597323776524288
author Almuntashiri, Sultan
Han, Yohan
Zhu, Yin
Dutta, Saugata
Niazi, Sara
Wang, Xiaoyun
Siddiqui, Budder
Zhang, Duo
author_facet Almuntashiri, Sultan
Han, Yohan
Zhu, Yin
Dutta, Saugata
Niazi, Sara
Wang, Xiaoyun
Siddiqui, Budder
Zhang, Duo
author_sort Almuntashiri, Sultan
collection PubMed
description 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.
format Online
Article
Text
id pubmed-8583934
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-85839342021-11-12 CC16 Regulates Inflammation, ROS Generation and Apoptosis in Bronchial Epithelial Cells during Klebsiella pneumoniae Infection Almuntashiri, Sultan Han, Yohan Zhu, Yin Dutta, Saugata Niazi, Sara Wang, Xiaoyun Siddiqui, Budder Zhang, Duo Int J Mol Sci Article 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. MDPI 2021-10-24 /pmc/articles/PMC8583934/ /pubmed/34768890 http://dx.doi.org/10.3390/ijms222111459 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Almuntashiri, Sultan
Han, Yohan
Zhu, Yin
Dutta, Saugata
Niazi, Sara
Wang, Xiaoyun
Siddiqui, Budder
Zhang, Duo
CC16 Regulates Inflammation, ROS Generation and Apoptosis in Bronchial Epithelial Cells during Klebsiella pneumoniae Infection
title CC16 Regulates Inflammation, ROS Generation and Apoptosis in Bronchial Epithelial Cells during Klebsiella pneumoniae Infection
title_full CC16 Regulates Inflammation, ROS Generation and Apoptosis in Bronchial Epithelial Cells during Klebsiella pneumoniae Infection
title_fullStr CC16 Regulates Inflammation, ROS Generation and Apoptosis in Bronchial Epithelial Cells during Klebsiella pneumoniae Infection
title_full_unstemmed CC16 Regulates Inflammation, ROS Generation and Apoptosis in Bronchial Epithelial Cells during Klebsiella pneumoniae Infection
title_short CC16 Regulates Inflammation, ROS Generation and Apoptosis in Bronchial Epithelial Cells during Klebsiella pneumoniae Infection
title_sort cc16 regulates inflammation, ros generation and apoptosis in bronchial epithelial cells during klebsiella pneumoniae infection
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8583934/
https://www.ncbi.nlm.nih.gov/pubmed/34768890
http://dx.doi.org/10.3390/ijms222111459
work_keys_str_mv AT almuntashirisultan cc16regulatesinflammationrosgenerationandapoptosisinbronchialepithelialcellsduringklebsiellapneumoniaeinfection
AT hanyohan cc16regulatesinflammationrosgenerationandapoptosisinbronchialepithelialcellsduringklebsiellapneumoniaeinfection
AT zhuyin cc16regulatesinflammationrosgenerationandapoptosisinbronchialepithelialcellsduringklebsiellapneumoniaeinfection
AT duttasaugata cc16regulatesinflammationrosgenerationandapoptosisinbronchialepithelialcellsduringklebsiellapneumoniaeinfection
AT niazisara cc16regulatesinflammationrosgenerationandapoptosisinbronchialepithelialcellsduringklebsiellapneumoniaeinfection
AT wangxiaoyun cc16regulatesinflammationrosgenerationandapoptosisinbronchialepithelialcellsduringklebsiellapneumoniaeinfection
AT siddiquibudder cc16regulatesinflammationrosgenerationandapoptosisinbronchialepithelialcellsduringklebsiellapneumoniaeinfection
AT zhangduo cc16regulatesinflammationrosgenerationandapoptosisinbronchialepithelialcellsduringklebsiellapneumoniaeinfection