Mycoplasma pneumoniae Modulates STAT3-STAT6/EGFR-FOXA2 Signaling To Induce Overexpression of Airway Mucins
| Autor: | Gee W. Lau, Jinfeng Miao, Li Yu Mei, Yonghua Hao, Ryan J. Lee, Zhizhou Kuang, Shawn Choe, Susie Kim, Duncan C. Krause, Jia Jing |
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| Rok vydání: | 2014 |
| Předmět: |
STAT3 Transcription Factor
Mycoplasma pneumoniae Immunology Mucin 5AC medicine.disease_cause Microbiology Cystic fibrosis Pneumonia Mycoplasma medicine Animals Humans Secretion STAT3 Cells Cultured STAT6 Cellular Microbiology: Pathogen-Host Cell Molecular Interactions biology Gene Expression Profiling Mucin Mucins Epithelial Cells respiratory system medicine.disease Mucin-5B Mucus respiratory tract diseases ErbB Receptors Mice Inbred C57BL Disease Models Animal Infectious Diseases Host-Pathogen Interactions Hepatocyte Nuclear Factor 3-beta biology.protein Parasitology Signal transduction STAT6 Transcription Factor Signal Transduction |
| Zdroj: | Infection and Immunity. 82:5246-5255 |
| ISSN: | 1098-5522 0019-9567 |
| DOI: | 10.1128/iai.01989-14 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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