Bifidobacterium Lactis sp. 420 up-regulates cyclooxygenase (Cox)-1 and down-regulates Cox-2 gene expression in a Caco-2 cell culture model.
Cyclooxygenases (Cox) -1 and -2 play important roles in gastrointestinal health; chronic overexpression of Cox-2 is associated with inflammatory and cancerous disease, whereas Cox-1 is expressed constitutively. We studied the effects of two probiotic (Bifidobacterium lactis sp. 420 and Lactobacillus acidophilus) and two control microorganisms (Escherichia coli and Salmonella enteritidis) and four microbial metabolites (acetate, butyrate, lactate and propionate) on the expression levels of the Cox isoforms in the enterocyte-like cell line Caco-2. Butyrate, which is anticarcinogenic, resulted in an 85% down-regulation of Cox-2 and a 37-fold increase in Cox-1 transcription. Propionate gave similar results (72% reduction of Cox-2, 23-fold induction of Cox-1), but lactate and acetate had no effect on Cox expression profile. Bifidobacterium sp. 420, which produces acetate and lactate but no butyrate or propionate, shared the Cox-1-increasing and Cox-2-silencing properties of butyrate and propionate, whereas L. acidophilus was similar to E. coli and S. enteritidis in having no effect on the Cox-1/Cox-2 ratio. For the first time, we therefore demonstrate evidence for a direct relationship between a probiotic bacterial strain and host Cox expression profile, suggesting that modulation of Cox expression may be an important factor in the potential anti-inflammatory and anticarcinogenic properties of some probiotics.
Nurmi
Jussi T
JT
Danisco Innovation, Enteromix Research, Sokeritehtaantie 20, 02460 Kantvik, Finland. jussi.nurmi@utu.fi
Puolakkainen
Pauli A
PA
Rautonen
Nina E
NE
D000085:Acetates / Q000494:pharmacology; D001644:Bifidobacterium / Q000201:enzymology* / Q000235:genetics; D002087:Butyrates / Q000494:pharmacology; D018938:Caco-2 Cells; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D007527:Isoenzymes; D019344:Lactic Acid / Q000494:pharmacology; D008565:Membrane Proteins; D019936:Probiotics; D011422:Propionates / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
D000085:Acetates; D002087:Butyrates; D007527:Isoenzymes; D008565:Membrane Proteins; D011422:Propionates; D019344:Lactic Acid; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases