Document Detail


Heme oxygenase-1 signals are involved in preferential inhibition of pro-inflammatory cytokine release by surfactin in cells activated with Porphyromonas gingivalis lipopolysaccharide.
MedLine Citation:
PMID:  20833156     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Porphyromonas gingivalis is considered the major pathogen of periodontal disease, which leads to chronic inflammation in oral tissues. P. gingivalis-produced lipopolysaccharide (LPS) is a key factor in the development of periodontitis. It is established that surfactin produced by Bacillus subtilis confers anti-inflammatory properties. However, the underlying mechanisms responsible for surfactin-induced anti-inflammatory actions in the context of periodontitis are poorly understood. In this study, we investigated whether surfactin affected P. gingivalis LPS-induced pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin (IL)-1β, IL-6, and IL-12, and determined that it significantly inhibited their production. Surfactin-mediated inhibition was mainly due to blocked activation of P. gingivalis LPS-triggered nuclear factor-κB. We also examined whether the regulatory effect of surfactin on P. gingivalis LPS-stimulated human THP-1 macrophages was mediated by the induction of heme oxygenase-1 (HO-1) signals, and determined that surfactin also induced HO-1 mRNA and protein expression via activation of Nrf-2. Additionally, we found that small interfering RNA-mediated knock-down of Nrf-2 significantly inhibited surfactin-induced HO-1 expression. Furthermore, inhibition of phosphoinositide 3-kinase (PI3K)/Akt and extracellular signal-regulated kinase (ERK) significantly decreased surfactin-induced HO-1 expression, which is consistent with the suggestion that surfactin-induced HO-1 expression occurs via PI3K/Akt, ERK, and Nrf-2. Treatment with a selective inhibitor of HO-1 reversed the surfactin-mediated inhibition of pro-inflammatory cytokines, suggesting that surfactin induces anti-inflammatory effects by activating Nrf-2-mediated HO-1 induction via PI3K/Akt and ERK signaling. Collectively, these observations support the potential of surfactin as a candidate in strategies to prevent caries, periodontitis, or other inflammatory diseases.
Authors:
Sun Young Park; Young Hun Kim; Eun-Kyoung Kim; Eun Yeon Ryu; Sang-Joon Lee
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Publication Detail:
Type:  Journal Article     Date:  2010-09-15
Journal Detail:
Title:  Chemico-biological interactions     Volume:  188     ISSN:  1872-7786     ISO Abbreviation:  Chem. Biol. Interact.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-11-12     Completed Date:  2010-12-21     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0227276     Medline TA:  Chem Biol Interact     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  437-45     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.
Affiliation:
Pusan National University, Busan, Republic of Korea.
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MeSH Terms
Descriptor/Qualifier:
Active Transport, Cell Nucleus / drug effects
Cell Line
Cell Nucleus / drug effects,  metabolism
Cytokines / secretion*
Enzyme Activation / drug effects
Enzyme Induction / drug effects
Extracellular Signal-Regulated MAP Kinases / metabolism
Heme Oxygenase-1 / biosynthesis,  genetics,  metabolism*
Humans
Inflammation / metabolism,  pathology
Lipopeptides / pharmacology*
Lipopolysaccharides / pharmacology*
Macrophages / cytology,  drug effects*,  metabolism,  secretion
NF-E2-Related Factor 2 / metabolism
NF-kappa B / metabolism
Peptides, Cyclic / pharmacology*
Porphyromonas gingivalis / chemistry*
Proto-Oncogene Proteins c-akt / metabolism
RNA, Messenger / genetics,  metabolism
Signal Transduction / drug effects*
Up-Regulation / drug effects
Chemical
Reg. No./Substance:
0/Cytokines; 0/Lipopeptides; 0/Lipopolysaccharides; 0/NF-E2-Related Factor 2; 0/NF-kappa B; 0/Peptides, Cyclic; 0/RNA, Messenger; 24730-31-2/surfactin peptide; EC 1.14.99.3/Heme Oxygenase-1; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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