Cc16 regulates inflammation, ros generation and apoptosis in bronchial epithelial cells during klebsiella pneumoniae infection

Sultan Almuntashiri, Yohan Han, Yin Zhu, Saugata Dutta, Sara Niazi, Xiaoyun Wang, Budder Siddiqui, Duo Zhang

Research output: Contribution to journalArticlepeer-review

Abstract

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 overex-pression of CC16 reduced reactive oxygen species (ROS) levels and protected BEAS-2B cells from K. pneu-induced apoptosis.

Original languageEnglish (US)
Article number11459
JournalInternational journal of molecular sciences
Volume22
Issue number21
DOIs
StatePublished - Nov 1 2021

Keywords

  • Bacterial pneumonia
  • Cell death
  • Innate immunity
  • Lung injury
  • NF-κB pathway
  • SCGB1A1

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Fingerprint

Dive into the research topics of 'Cc16 regulates inflammation, ros generation and apoptosis in bronchial epithelial cells during klebsiella pneumoniae infection'. Together they form a unique fingerprint.

Cite this