Propionic Acid Stimulates Superoxide Generation in Human Neutrophils

Abstract

Short-chain carboxylic acids are the metabolic by-products of pathogenic anaerobic bacteria and are found at sites of infection in millimolar quantities. We previously reported that propionic acid, one of the short-chain carboxylic acids, induces an increase in intracellular Ca2+ ([Ca2+]i) in human neutrophils. Here we investigate the effect of propionic acid on superoxide generation in human neutrophils. Propionic acid (10 mm) induced inositol 1,4, 5-trisphosphate (IP3) formation and a rapidly transient increase in [Ca2+]i, but not superoxide generation, whereas 1 microm formylmethionyl-leucyl-phenylalanine (fMLP), a widely used neutrophil-stimulating bacterial peptide, stimulated not only IP3 formation and Ca2+ mobilization but also superoxide generation. The IP3 level induced by propionic acid was slightly lower than that induced by fMLP. The transient increase in [Ca2+]i induced by propionic acid immediately returned to the basal level, whereas a sustained increase in [Ca2+]i, which was higher than the basal level, following a transient increase in [Ca2+]i was induced by fMLP. The peak level induced by propionic acid was lower than that with fMLP. In the absence of extracellular Ca2+, thapsigargin, a potent inhibitor of endoplasmic reticulum Ca2+-ATPase, induced an increase in [Ca2+]i even after propionic acid stimulation, but not after fMLP. The Ca2+ ionophore A23187 and thapsigargin induced superoxide generation by themselves. Propionic acid enhanced the superoxide generating effect of A23187 and thapsigargin. These results suggest that Ca2+ mobilization induced by propionic acid is much weaker than that with fMLP, and propionic acid is able to generate superoxide in the presence of a Ca2+ ionophore and a Ca2+ influx activator.

The Role of the Microbial Metabolites Including Tryptophan Catabolites and Short Chain Fatty Acids in the Pathophysiology of Immune-Inflammatory and Neuroimmune Disease

“…The effect of propionate or butyrate on reactive oxygen species synthesis by neutrophils, on the other hand, remains controversial. Some authors have reported increased reactive oxygen species production by SCFAs [124,125], while others have demonstrated inhibitory effects [126,127]. Controversy also surrounds the possible impact of SCFAs on microglial production of reactive oxygen species, NO, prostaglandin-E2, etc.…”

Bacterial Neuroactive Compounds Produced by Psychobiotics

“…They also play a role in cell signalling [91] and neurotransmitter synthesis and release [92]. Moreover, SCFA have been shown to increase the synthesis of dopamine and its related catecholamines through induction of tyrosine hydroxylase, a key enzyme in the synthesis of catecholamines [93].…”

Short-chain fatty acids act as antiinflammatory mediatorsby regulating prostaglandin E2 and cytokines

“…Acetate, propionate and butyrate represent the most often described SCFAs that are capable of immune activation. SCFAs affect neutrophil function and migration [12][13][14][15] , and inhibit tumor necrosis factor-α (TNF-α) or interleukin-1β (IL-1β)-induced vascular cell adhesion molecule-1 (and intercellular adhesion molecule-1) surface expression [16] . In addition, SCFAs reduce adherence of monocytes or lymphocytes to cytokinestimulated human umbilical vein endothelial cells [17] , and inhibit interferon-γ (IFN-γ) signaling [18,19] , a possible regulator of inflammation in inflammatory bowel disease (IBD).…”