title: Short-chain fatty acids induce pro-inflammatory cytokine production alone and in combination with toll-like receptor ligands.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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: Department of Immunology/Microbiology, Rush University Medical Center, Chicago, IL, USA.
authors: Paria
authors: P
authors: Mirmonsef
authors: Mohammad R
authors: MR
authors: Zariffard
authors: Douglas
authors: D
authors: Gilbert
authors: Hadijat
authors: H
authors: Makinde
authors: Alan L
authors: AL
authors: Landay
authors: Greg T
authors: GT
authors: Spear
mesh_terms: D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology*; D005232:Fatty Acids, Volatile / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D008024:Ligands; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology; D017382:Reactive Oxygen Species / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000276:immunology*; D051199:Toll-Like Receptor 7 / Q000276:immunology*; D016585:Vaginosis, Bacterial / Q000276:immunology*
chemical_list: D016207:Cytokines; D005232:Fatty Acids, Volatile; D008024:Ligands; D017382:Reactive Oxygen Species; C495345:TLR4 protein, human; C495348:TLR7 protein, human; D051197:Toll-Like Receptor 4; D051199:Toll-Like Receptor 7