Document Detail


Short-chain fatty acids induce pro-inflammatory cytokine production alone and in combination with toll-like receptor ligands.
MedLine Citation:
PMID:  22059850     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PROBLEM: Short-chain fatty acids (SCFAs), produced at relatively high levels by anaerobic bacteria in bacterial vaginosis (BV), are believed to be anti-inflammatory. BV, a common alteration in the genital microbiota associated with increased susceptibility to HIV infection, is characterized by increased levels of both pro-inflammatory cytokines and SCFAs. We investigated how SCFAs alone or together with Toll-like receptor (TLR) ligands affected pro-inflammatory cytokine secretion.
METHOD OF STUDY: Cytokines were measured by ELISA. Flow was used for phenotyping and reactive oxygen species (ROS) measurement.
RESULTS: Short-chain fatty acids, at 20 mM, induced interleukin (IL)-8, IL-6, and IL-1β release, while lower levels (0.02-2 mM) did not induce cytokine secretion. Levels >20 mM were toxic to cells. Interestingly, lower levels of SCFAs significantly enhanced TLR2 ligand- and TLR7 ligand-induced production of IL-8 and TNFα in a time- and dose-dependent manner, but had little effect on lipopolysaccharide-induced cytokine release. SCFAs mediated their effects on pro-inflammatory cytokine production at least in part by inducing the generation of ROS.
CONCLUSION: Our data suggest that SCFAs, especially when combined with specific TLR ligands, contribute to a pro-inflammatory milieu in the lower genital tract and help further our understanding of how BV affects susceptibility to microbial infections.
Authors:
Paria Mirmonsef; Mohammad R Zariffard; Douglas Gilbert; Hadijat Makinde; Alan L Landay; Greg T Spear
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2011-11-08
Journal Detail:
Title:  American journal of reproductive immunology (New York, N.Y. : 1989)     Volume:  67     ISSN:  1600-0897     ISO Abbreviation:  Am. J. Reprod. Immunol.     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-04-11     Completed Date:  2012-08-07     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  8912860     Medline TA:  Am J Reprod Immunol     Country:  Denmark    
Other Details:
Languages:  eng     Pagination:  391-400     Citation Subset:  IM    
Copyright Information:
© 2011 John Wiley & Sons A/S.
Affiliation:
Department of Immunology/Microbiology, Rush University Medical Center, Chicago, IL, USA.
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MeSH Terms
Descriptor/Qualifier:
Cells, Cultured
Cytokines / immunology*
Fatty Acids, Volatile / pharmacology*
Female
Humans
Leukocytes, Mononuclear / drug effects,  immunology
Ligands
Male
Neutrophils / drug effects,  immunology
Reactive Oxygen Species / immunology
Toll-Like Receptor 4 / immunology*
Toll-Like Receptor 7 / immunology*
Vaginosis, Bacterial / immunology*
Grant Support
ID/Acronym/Agency:
P01 AI082971/AI/NIAID NIH HHS; P01 AI082971/AI/NIAID NIH HHS; P01 AI082971-01/AI/NIAID NIH HHS; P30 AI082151/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Cytokines; 0/Fatty Acids, Volatile; 0/Ligands; 0/Reactive Oxygen Species; 0/TLR4 protein, human; 0/TLR7 protein, human; 0/Toll-Like Receptor 4; 0/Toll-Like Receptor 7
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