Differential microRNA (miRNA) expression could explain microbial tolerance in a novel chronic peritonitis model

We observed persistent peritoneal bacteria despite a transient early innate immune response to intraperitoneal (IP) Klebsiella pneumoniae. Pretreatment with LPS prior to peritonitis induced a tolerant pattern of pro-inflammatory cytokine protein production over 72 h, but not at the mRNA level. Micro...

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Bibliographic Details
Published in:Innate immunity (London, England) England), 2013-04, Vol.19 (2), p.203-212
Main Authors: Kanaan, Ziad, Barnett, Rebecca, Gardner, Sarah, Keskey, Bobby, Druen, Devin, Billeter, Adrian, Cheadle, William G
Format: Article
Language:English
Subjects:
Animals
Cells, Cultured
Chronic Disease
Computational Biology
Cytokines - metabolism
Disease Models, Animal
High Mobility Group Proteins - genetics
High Mobility Group Proteins - metabolism
Humans
Immune Tolerance
Inflammation Mediators - metabolism
Klebsiella Infections - complications
Klebsiella Infections - immunology
Klebsiella pneumoniae
Klebsiella pneumoniae - immunology
Male
Mice
Mice, Inbred C57BL
MicroRNAs - genetics
MicroRNAs - immunology
MicroRNAs - metabolism
NF-kappa B - metabolism
Peritonitis - etiology
Peritonitis - immunology
Repressor Proteins - genetics
Repressor Proteins - metabolism
RNA, Messenger - genetics
RNA, Messenger - immunology
RNA, Messenger - metabolism
Signal Transduction - immunology
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Summary:We observed persistent peritoneal bacteria despite a transient early innate immune response to intraperitoneal (IP) Klebsiella pneumoniae. Pretreatment with LPS prior to peritonitis induced a tolerant pattern of pro-inflammatory cytokine protein production over 72 h, but not at the mRNA level. MicroRNAs (miRNAs) regulate inflammatory cytokines and may explain this paradox. After pretreatment with IP LPS or saline, C57BL/6 mice were given 103 CFU of K. pneumoniae IP. Total RNA was isolated from peritoneal exudate cells (4 h, 24 h and 48 h following infection). mRNA and miRNA expression levels were detected and bioinformatics pathway analysis was performed, followed by measuring TNF-α, IL-1β, IL-6 and High-mobility Group Box 1 (HMBG1) protein levels. Of 88 miRNAs studied, 30 were significantly dysregulated at all time points in the LPS-pretreated group, including MiR-155, -146a, -142-3p, -299, and -200c -132 and -21. TNF-α, regulated by miR-155 and miR-146a, was decreased in the LPS-pretreated group at all time points (P 
ISSN:1753-4259
1753-4267
DOI:10.1177/1753425912460557