Short-Chain Fatty Acids Induce Pro-Inflammatory Cytokine Production Alone and in Combination with Toll-Like Receptor Ligands

Paria Mirmonsef, Mohammad R. Zariffard, Douglas Gilbert, Hadijat Makinde, Alan L. Landay, Greg T. Spear*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

81 Scopus citations

Abstract

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 20mm, induced interleukin (IL)-8, IL-6, and IL-1β release, while lower levels (0.02-2mm) did not induce cytokine secretion. Levels >20mm 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.

Original languageEnglish (US)
Pages (from-to)391-400
Number of pages10
JournalAmerican Journal of Reproductive Immunology
Volume67
Issue number5
DOIs
StatePublished - May 2012
Externally publishedYes

Keywords

  • Bacterial vaginosis
  • Inflammation
  • Short-chain fatty acids

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Reproductive Medicine
  • Obstetrics and Gynecology

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