Butyric acid stimulates bovine neutrophil functions and potentiates the effect of platelet activating factor.
Increased short-chain fatty acid (SCFA) production is associated with subacute ruminal acidosis (SARA) and activation of inflammatory processes. In humans and rodents, SCFAs modulate inflammatory responses in the gut via free fatty acid receptor 2 (FFA2). In bovines, butyric acid is one of the most potent FFA2 agonists. Its expression in bovine neutrophils has recently been demonstrated, suggesting a role in innate immune response in cattle. This study aimed to evaluate if butyric acid modulates oxidative and non-oxidative functions or if it can potentiate other inflammatory mediators in bovine neutrophils. Our results showed that butyric acid can activate bovine neutrophils, inducing calcium (Ca(2+)) influx and mitogen-activated protein kinase (MAPK) phosphorylation, two second messengers involved in FFA2 activation. Ca(2+) influx induced by butyric acid was dependent on the extracellular and intracellular Ca(2+) source and phospholipase C (PLC) activation. Butyric acid alone had no significant effect on reactive oxygen species (ROS) production and chemotaxis; however, a priming effect on platelet-activating factor (PAF), a potent inflammatory mediator, was observed. Butyric acid increased CD63 expression and induced the release of neutrophil granule markers matrix metalloproteinase-9 (MMP-9) and lactoferrin. Finally, we observed that butyric acid induced neutrophil extracellular trap (NET) formation without affecting cellular viability. These findings suggest that butyric acid, a component of the ruminal fermentative process, can modulate the innate immune response of ruminants.
Laboratory of Molecular Pharmacology, Institute of Pharmacology, Faculty of Veterinary Science, Universidad Austral de Chile, Valdivia, Chile.
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MD
Carretta
Laboratory of Molecular Pharmacology, Institute of Pharmacology, Faculty of Veterinary Science, Universidad Austral de Chile, Valdivia, Chile.
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AI
Hidalgo
Laboratory of Molecular Pharmacology, Institute of Pharmacology, Faculty of Veterinary Science, Universidad Austral de Chile, Valdivia, Chile.
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J
Burgos
Laboratory of Molecular Pharmacology, Institute of Pharmacology, Faculty of Veterinary Science, Universidad Austral de Chile, Valdivia, Chile.
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L
Opazo
Laboratory of Molecular Pharmacology, Institute of Pharmacology, Faculty of Veterinary Science, Universidad Austral de Chile, Valdivia, Chile.
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L
Castro
Laboratory of Molecular Pharmacology, Institute of Pharmacology, Faculty of Veterinary Science, Universidad Austral de Chile, Valdivia, Chile.
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MA
Hidalgo
Laboratory of Cellular Pathology, Institute of Anatomy, Histology and Pathology, Faculty of Medicine, Universidad Austral de Chile, Valdivia, Chile.
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CD
Figueroa
Institute of Parasitology, Biomedical Research Center Seltersberg, Justus Liebig University Giessen, Giessen, Germany.
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A
Taubert
Institute of Parasitology, Biomedical Research Center Seltersberg, Justus Liebig University Giessen, Giessen, Germany.
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C
Hermosilla
Laboratory of Molecular Pharmacology, Institute of Pharmacology, Faculty of Veterinary Science, Universidad Austral de Chile, Valdivia, Chile. Electronic address: rburgos1@uach.cl.
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RA
Burgos
D000818:Animals; D020148:Butyric Acid / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002417:Cattle / Q000276:immunology*; D002634:Chemotaxis, Leukocyte; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D065206:Extracellular Traps / Q000187:drug effects; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D010972:Platelet Activating Factor / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D005230:Fatty Acids, Nonesterified; D010972:Platelet Activating Factor; D017382:Reactive Oxygen Species; D020148:Butyric Acid; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D002118:Calcium
Butyric acid; Calcium; MAPK; Neutrophil extracellular traps; Neutrophils granules; Radical oxygen species