Short chain fatty acids induce IL-1β production: The role of monocarboxylate transporters (MCTs) (117.16)

Abstract

Short chain fatty acids (SCFAs) are products of anaerobic bacteria at mucosal sites, such as the female genital tract in bacterial vaginosis (BV). IL-1β, a potent proinflammatory cytokine, is found at elevated levels in the vaginal fluids of BV+ women. We recently found that SCFAs induce IL-1β in monocytes. Here, we tested whether SCFAs could control IL-1β production by either: 1) inducing pro IL-1β in the cytoplasm, and/or 2) causing inflammasome activation and release of IL-1β by acting as a “second” danger signal. We found that exposing peripheral blood mononuclear cells (PBMCs) for 24-hours to physiological levels of either acetic or butyric acid resulted in a modest increase in IL-1β levels in vitro. The release of IL-1β was more robust and occurred more rapidly when PBMCs were treated with SCFAs first, followed by exogenous ATP as a “danger” signal. SCFAs themselves were not potent danger signals as they failed to increase the release of LPS-induced pro IL-1β. Since SCFAs can enter cells via MCTs, we blocked these transporters using pharmacological agents and found that MCTs were necessary for SCFA-mediated IL-1β production. These findings show that SCFAs can induce cytoplasmic pro IL-1β production and that their effects are MCT-dependent. Because IL-1β is an important proinflammatory mediator, these results enhance our understanding of how SCFAs may contribute to the inflammatory environment seen in BV.