title: Short-chain carboxylic acids produced by gram-negative anaerobic bacteria can accelerate or delay polymorphonuclear leukocyte apoptosis in vitro.
abstract: BACKGROUND
  Short-chain carboxylic acids (SCCA) are metabolic byproducts of anaerobic subgingival bacteria associated with human periodontal disease. We examined the effect of 4 SCCA (butyric, propionic, succinic, and lactic acids) on human polymorphonuclear leukocyte (PMN) apoptosis over the range of concentrations (1 to 30 mM) found in the diseased periodontium.
  
  
  METHODS
  PMN suspensions were incubated at 37 degrees C with medium alone (control) or one of the 4 SCCA at concentrations of 1, 5, or 30 mM. Aliquots were withdrawn hourly to assess apoptosis and viability by fluorescence microscopy.
  
  
  RESULTS
  Relative to untreated controls, PMN incubated for at least 5 hours with 1 mM butyric or propionic acids exhibited significant delays in apoptosis (P<0.05), while those incubated with succinic or lactic acids exhibited no significant differences from controls (P>0.05). At a concentration of 5 mM, propionic, succinic, and lactic acids had little effect on apoptosis (P>0.05), but butyric acid significantly accelerated apoptotic changes (P<0.05). At 30 mM, all SCCA except lactic acid significantly accelerated apoptosis (P<0.05). Incubation with SCCA did not adversely affect cell viability (typically >98%). Lysates from PMN incubated 6 hours with 30 mM butyric or propionic acids contained significantly more caspase-3 activity than lysates from untreated control PMN (P<0.05). Moreover, pretreatment with a specific inhibitor of caspase-3 blocked acceleration of PMN apoptosis by butyric or propionic acids (P<0.05).
  
  
  CONCLUSIONS
  Low concentrations of butyric or propionic acids delay PMN apoptosis and extend their functional lifespan, while higher concentrations accelerate apoptosis through a mechanism that appears to involve caspase-3.
authors.affiliation: Department of Periodontology, College of Dentistry, The Ohio State University Health Sciences Center, Columbus, USA.
authors.forename: H W
authors.initials: HW
authors.lastname: Stehle
authors.forename: B
authors.initials: B
authors.lastname: Leblebicioglu
authors.forename: J D
authors.initials: JD
authors.lastname: Walters
mesh_terms: D000704:Analysis of Variance; D017209:Apoptosis / Q000187:drug effects*; D001421:Bacteria, Anaerobic / Q000737:chemistry*; D020148:Butyric Acid / Q000494:pharmacology; D002264:Carboxylic Acids / Q000494:pharmacology*; D053148:Caspase 3; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006090:Gram-Negative Bacteria / Q000737:chemistry; D006801:Humans; D019344:Lactic Acid / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology*; D011422:Propionates / Q000494:pharmacology; D019802:Succinic Acid / Q000494:pharmacology
chemical_list: D002264:Carboxylic Acids; D061945:Caspase Inhibitors; D011422:Propionates; D020148:Butyric Acid; D019344:Lactic Acid; D019802:Succinic Acid; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; C029658:propionic acid