Nitrated oleic acid up-regulates PPARgamma and attenuates experimental inflammatory bowel disease.

Nitric oxide and its metabolites undergo nitration reactions with unsaturated fatty acids during oxidative inflammatory conditions, forming electrophilic nitro-fatty acid derivatives. These endogenous electrophilic mediators activate anti-inflammatory signaling reactions, serving as high-affinity ligands for peroxisome proliferator-activated receptor gamma (PPARgamma). Here we examined the therapeutic effects of 9- or 10-nitro-octadecenoic oleic acid (OA-NO(2)) and native oleic acid (OA) in a mouse model of colitis.

Gastroprotective and blood pressure lowering effects of dietary nitrate are abolished by an antiseptic mouthwash.

Recently, it has been suggested that the supposedly inert nitrite anion is reduced in vivo to form bioactive nitric oxide with physiological and therapeutic implications in the gastrointestinal and cardiovascular systems. Intake of nitrate-rich food such as vegetables results in increased levels of circulating nitrite in a process suggested to involve nitrate-reducing bacteria in the oral cavity. Here we investigated the importance of the oral microflora and dietary nitrate in regulation of gastric mucosal defense and blood pressure.

The increase in plasma nitrite after a dietary nitrate load is markedly attenuated by an antibacterial mouthwash.

Recent studies surprisingly show that dietary inorganic nitrate, abundant in vegetables, can be metabolized in vivo to form nitrite and then bioactive nitric oxide. A reduction in blood pressure was recently noted in healthy volunteers after dietary supplementation with nitrate; an effect consistent with formation of vasodilatory nitric oxide. Oral bacteria have been suggested to play a role in bioactivation of nitrate by first reducing it to the more reactive anion nitrite.

A mammalian functional nitrate reductase that regulates nitrite and nitric oxide homeostasis.

Inorganic nitrite (NO(2)(-)) is emerging as a regulator of physiological functions and tissue responses to ischemia, whereas the more stable nitrate anion (NO(3)(-)) is generally considered to be biologically inert. Bacteria express nitrate reductases that produce nitrite, but mammals lack these specific enzymes. Here we report on nitrate reductase activity in rodent and human tissues that results in formation of nitrite and nitric oxide (NO) and is attenuated by the xanthine oxidoreductase inhibitor allopurinol.

Protection from nonsteroidal anti-inflammatory drug (NSAID)-induced gastric ulcers by dietary nitrate.

Nitrate is abundant in our diet with particularly high levels in many vegetables. Ingested nitrate is concentrated in saliva and reduced to nitrite by bacteria in the oral cavity. We recently reported that application of nitrite-containing saliva to the gastric mucosa increases superficial blood flow and mucus generation via acid-catalyzed formation of bioactive nitrogen oxides including nitric oxide.

Dietary nitrate increases gastric mucosal blood flow and mucosal defense.

Salivary nitrate from dietary or endogenous sources is reduced to nitrite by oral bacteria. In the acidic stomach, nitrite is further reduced to bioactive nitrogen oxides, including nitric oxide (NO). In this study, we investigated the gastroprotective role of nitrate intake and of luminally applied nitrite against provocation with diclofenac and taurocholate.

Generation of NO by probiotic bacteria in the gastrointestinal tract.

Probiotic bacteria elicit a number of beneficial effects in the gut but the mechanisms for these health promoting effects are not entirely understood. Recent in vitro data suggest that lactobacilli can utilise nitrate and nitrite to generate nitric oxide, a gas with immunomodulating and antibacterial properties. Here we further characterised intestinal NO generation by bacteria.

Cardioprotective effects of vegetables: is nitrate the answer?

A diet rich in fruits and vegetables is associated with a lower risk of certain forms of cancer and cardiovascular disease, but the mechanisms behind this protection are not completely understood. Recent epidemiological studies suggest a cardioprotective action afforded specifically by green leafy vegetables. We here propose that these beneficial effects are related to the high content of inorganic nitrate, which in concert with symbiotic bacteria in the oral cavity is converted into nitrite, nitric oxide, and secondary reaction products with vasodilating and tissue-protective properties.

The Wnt/beta-catenin signaling pathway targets PPARgamma activity in colon cancer cells.

Control of colon cell fate in adenocarcinomas is disrupted, in part, due to aberrant Wnt/beta-catenin signaling. The nuclear receptor peroxisome proliferator-activated receptor-gamma (PPARgamma) has been implicated in the development of colon cancers. In the adenomatous polyposis coli multiple intestinal neoplasia (APCMin) mouse cancer model, PPARgamma expression in the colonic mucosa is markedly altered.

Commensal anaerobic gut bacteria attenuate inflammation by regulating nuclear-cytoplasmic shuttling of PPAR-gamma and RelA.

The human gut microflora is important in regulating host inflammatory responses and in maintaining immune homeostasis. The cellular and molecular bases of these actions are unknown. Here we describe a unique anti-inflammatory mechanism, activated by nonpathogenic bacteria, that selectively antagonizes transcription factor NF-kappaB.

Impaired expression of peroxisome proliferator-activated receptor gamma in ulcerative colitis.

Background & Aims: The peroxisome proliferator-activated receptor gamma (PPAR gamma) has been proposed as a key inhibitor of colitis through attenuation of nuclear factor kappa B (NF-kappa B) activity. In inflammatory bowel disease, activators of NF-kappa B, including the bacterial receptor toll-like receptor (TLR)4, are elevated. We aimed to determine the role of bacteria and their signaling effects on PPAR gamma regulation during inflammatory bowel disease (IBD).