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The NLRP3 Inflammasome is not Activated in Airway Smooth Muscle Upon TLR2 Ligation.
MedLine Citation:
PMID:  23614732     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Inflammasomes have emerged as playing key roles in inflammation and innate immunity. A growing body of evidence has suggested that the nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3) inflammasome is important in chronic airway diseases such as asthma and COPD. Inflammasome activation results, in part, in pro-IL-1β processing and secretion of the pro-inflammatory cytokine IL-1β. Because asthma exacerbations are associated with elevated levels of secreted IL-1β we addressed whether the NLRP3 inflammasome is activated under in vitro conditions that mimic infectious exacerbation in asthma. Primary cultures of airway smooth muscle (ASM) cells were treated with infectious stimuli (mimicked using the TLR2 agonist Pam3CSK4, a synthetic bacterial lipopeptide). While Pam3CSK4 robustly upregulated ASM cytokine expression in response to TNFα and significantly enhanced IL-1β mRNA expression, we were unable to detect IL-1β in the cell supernatants. Thus, IL-1β was not secreted and therefore unable to act in an autocrine manner to promote amplification of ASM inflammatory responses. Moreover, TLR2 ligation did not enhance NLRP3 or caspase-1 expression in ASM cells, and NLRP3 and caspase-1 protein was not present in the airway smooth muscle layer of tracheal sections from human donors. In conclusion, these data demonstrate that enhanced synthetic function of ASM cells, induced by infectious exacerbation of airway inflammation, is NLRP3 inflammasome- and IL-1β-independent. Activation of the NLRP3 inflammasome by invading pathogens may prove cell-type specific in exacerbation of airway inflammation in asthma.
Authors:
Jeremy A Hirota; Hanna Im; Md Mostafizur Rahman; Nowshin N Rumzhum; Melanie Manetsch; Chris Pascoe; Kristin Bunge; Hatem Alkhouri; Brian G Oliver; Alaina J Ammit
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-4-24
Journal Detail:
Title:  American journal of respiratory cell and molecular biology     Volume:  -     ISSN:  1535-4989     ISO Abbreviation:  Am. J. Respir. Cell Mol. Biol.     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-4-25     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8917225     Medline TA:  Am J Respir Cell Mol Biol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
UBC James Hogg Research Centre Heart + Lung Institute, St Pauls Hospital, Vancouver, British Columbia, Canada ; Jeremy.Hirota@hli.ubc.ca.
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