Cigarette smoke inhibits LPS-induced FABP5 expression by preventing c-Jun binding to the FABP5 promoter.
Cigarette smoking is the primary cause of chronic obstructive pulmonary disease (COPD) with repeated and sustained infections linked to disease pathogenesis and exacerbations. The airway epithelium constitutes the first line of host defense against infection and is known to be impaired in COPD. We h...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2017-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5436865?pdf=render |
| _version_ | 1819042116836261888 |
|---|---|
| author | Deviyani Rao Anne-Laure Perraud Carsten Schmitz Fabienne Gally |
| author_facet | Deviyani Rao Anne-Laure Perraud Carsten Schmitz Fabienne Gally |
| author_sort | Deviyani Rao |
| collection | DOAJ |
| description | Cigarette smoking is the primary cause of chronic obstructive pulmonary disease (COPD) with repeated and sustained infections linked to disease pathogenesis and exacerbations. The airway epithelium constitutes the first line of host defense against infection and is known to be impaired in COPD. We have previously identified Fatty Acid Binding Protein 5 (FABP5) as an important anti-inflammatory player during respiratory infections and showed that overexpression of FABP5 in primary airway epithelial cells protects against bacterial infection and inflammation. While cigarette smoke down regulates FABP5 expression, its mechanism remains unknown. In this report, we have identified three putative c-Jun binding sites on the FABP5 promoter and show that cigarette smoke inhibits the binding of c-Jun to its consensus sequence and prevents LPS-induced FABP5 expression. Using chromatin immunoprecipitation, we have determined that c-Jun binds the FABP5 promoter when stimulated with LPS but the presence of cigarette smoke greatly reduces this binding. Furthermore, cigarette smoke or a mutation in the c-Jun binding site inhibits LPS-induced FABP5 promoter activity. These data demonstrate that cigarette smoke interferes with FABP5 expression in response to bacterial infection. Thus, functional activation of FABP5 may be a new therapeutic strategy when treating COPD patients suffering from exacerbations. |
| first_indexed | 2024-12-21T09:35:47Z |
| format | Article |
| id | doaj.art-49c0262af65646719ddbe685492b1ce3 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-21T09:35:47Z |
| publishDate | 2017-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-49c0262af65646719ddbe685492b1ce32022-12-21T19:08:38ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01125e017802110.1371/journal.pone.0178021Cigarette smoke inhibits LPS-induced FABP5 expression by preventing c-Jun binding to the FABP5 promoter.Deviyani RaoAnne-Laure PerraudCarsten SchmitzFabienne GallyCigarette smoking is the primary cause of chronic obstructive pulmonary disease (COPD) with repeated and sustained infections linked to disease pathogenesis and exacerbations. The airway epithelium constitutes the first line of host defense against infection and is known to be impaired in COPD. We have previously identified Fatty Acid Binding Protein 5 (FABP5) as an important anti-inflammatory player during respiratory infections and showed that overexpression of FABP5 in primary airway epithelial cells protects against bacterial infection and inflammation. While cigarette smoke down regulates FABP5 expression, its mechanism remains unknown. In this report, we have identified three putative c-Jun binding sites on the FABP5 promoter and show that cigarette smoke inhibits the binding of c-Jun to its consensus sequence and prevents LPS-induced FABP5 expression. Using chromatin immunoprecipitation, we have determined that c-Jun binds the FABP5 promoter when stimulated with LPS but the presence of cigarette smoke greatly reduces this binding. Furthermore, cigarette smoke or a mutation in the c-Jun binding site inhibits LPS-induced FABP5 promoter activity. These data demonstrate that cigarette smoke interferes with FABP5 expression in response to bacterial infection. Thus, functional activation of FABP5 may be a new therapeutic strategy when treating COPD patients suffering from exacerbations.http://europepmc.org/articles/PMC5436865?pdf=render |
| spellingShingle | Deviyani Rao Anne-Laure Perraud Carsten Schmitz Fabienne Gally Cigarette smoke inhibits LPS-induced FABP5 expression by preventing c-Jun binding to the FABP5 promoter. PLoS ONE |
| title | Cigarette smoke inhibits LPS-induced FABP5 expression by preventing c-Jun binding to the FABP5 promoter. |
| title_full | Cigarette smoke inhibits LPS-induced FABP5 expression by preventing c-Jun binding to the FABP5 promoter. |
| title_fullStr | Cigarette smoke inhibits LPS-induced FABP5 expression by preventing c-Jun binding to the FABP5 promoter. |
| title_full_unstemmed | Cigarette smoke inhibits LPS-induced FABP5 expression by preventing c-Jun binding to the FABP5 promoter. |
| title_short | Cigarette smoke inhibits LPS-induced FABP5 expression by preventing c-Jun binding to the FABP5 promoter. |
| title_sort | cigarette smoke inhibits lps induced fabp5 expression by preventing c jun binding to the fabp5 promoter |
| url | http://europepmc.org/articles/PMC5436865?pdf=render |
| work_keys_str_mv | AT deviyanirao cigarettesmokeinhibitslpsinducedfabp5expressionbypreventingcjunbindingtothefabp5promoter AT annelaureperraud cigarettesmokeinhibitslpsinducedfabp5expressionbypreventingcjunbindingtothefabp5promoter AT carstenschmitz cigarettesmokeinhibitslpsinducedfabp5expressionbypreventingcjunbindingtothefabp5promoter AT fabiennegally cigarettesmokeinhibitslpsinducedfabp5expressionbypreventingcjunbindingtothefabp5promoter |