Affiliation:
1. Department of Pathobiology, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA
2. College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, People's Republic of China
3. Department of Microbiology, University of Georgia, Athens, Georgia, USA
Abstract
ABSTRACT
Aberrant mucin secretion and accumulation in the airway lumen are clinical hallmarks associated with various lung diseases such as asthma, chronic obstructive pulmonary disease, and cystic fibrosis.
Mycoplasma pneumoniae
, long appreciated as one of the triggers of acute exacerbations of chronic pulmonary diseases, has recently been reported to promote excessive mucus secretion. However, the mechanism of mucin overproduction induced by
M. pneumoniae
remains unclear. This study aimed to determine the mechanism by which
M. pneumoniae
induces mucus hypersecretion by using
M. pneumoniae
infection of mouse lungs, human primary bronchial epithelial (NHBE) cells cultured at the air-liquid interface, and the conventionally cultured airway epithelial NCI-H292 cell line. We demonstrated that
M. pneumoniae
induced the expression of mucins MUC5AC and MUC5B by activating the STAT6-STAT3 and epidermal growth factor receptor (EGFR) signal pathways, which in turn downregulated FOXA2, a transcriptional repressor of mucin biosynthesis. The upstream stimuli of these pathways, including interleukin-4 (IL-4), IL-6, and IL-13, increased dramatically upon exposure to
M. pneumoniae
. Inhibition of the STAT6, STAT3, and EGFR signaling pathways significantly restored the expression of FOXA2 and attenuated the expression of airway mucins MUC5AC and MUC5B. Collectively, these studies demonstrated that
M. pneumoniae
induces airway mucus hypersecretion by modulating the STAT/EGFR-FOXA2 signaling pathways.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
Cited by
64 articles.
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