Toll-like receptor 9 signaling mediates the anti-inflammatory effects of probiotics in murine experimental colitis

Rachmilewitz, Daniel; Katakura, Kyoko; Karmeli, Fanny; Hayashi, Tomoko; Reinus, Constantin; Rudensky, Bernard; Akira, Shizuo; Takeda, Kiyoshi; Lee, Jongdae; Takabayashi, Kenji; Raz, Eyal

doi:10.1053/j.gastro.2003.11.019

Cited by 768 publications

(580 citation statements)

References 23 publications

Supporting

Mentioning

530

Contrasting

Unclassified

Order By: Relevance

“…Moreover, modulators of Toll like receptor (TLR) signalling have been considered for IBD ther apy 132 . CpG site containing oligonucleotides suppress immune cell activation and protect barrier function in experimental colitis via TLR9 signalling 133 . Finally, the TLR7 ligand imiquimod suppressed CD11c + den dritic cells and activated intestinal epithelial cells to produce antimicrobial peptides, resulting in reduced colitis activity 134 .…”

Section: T Cellmentioning

confidence: 99%

Current and emerging therapeutic targets for IBD

Neurath

2017

Nat Rev Gastroenterol Hepatol

485

376

View full text Add to dashboard Cite

Inflammatory bowel diseases (including IBD, exempli fied by Crohn's disease and ulcerative colitis) are chronic relapsing disorders affecting the gastrointestinal tract. IBD has a progressive and destructive nature and, there fore, can cause various complications including steno ses, abscesses, fistulas, extraintestinal manifestations and colitis associated neoplasias and cancer 1,2 . Thus, effective therapeutic approaches are of high clinical rele vance in patients with IBD. This Review summarizes current therapeutic strategies and highlights emerging new treatment approaches for IBD with special refer ence to the proposed molecular mechanisms of action of anti inflammatory drugs. Current IBD therapiesClassic anti-inflammatory drugs. 5 Aminosalicylates (5 ASAs) are important anti inflammatory drugs that are frequently used for anti inflammatory therapy in patients with ulcerative colitis 3 . By contrast, 5 ASA based drugs show little or no efficacy in inducing res olution of clinical symptoms and tissue inflammation in patients with Crohn's disease 4 .5 ASAs are effective for induction and mainten ance of remission in ulcerative colitis and might also reduce the risk of developing colitis associated tumours in these patients 5 . Several mechanisms of action for 5 ASAs have been proposed, including reduction of prostaglandin synthesis via inhibition of cyclooxygenase, suppression of proinflammatory cytokine production and oxygen free radicals, inhib ition of lipoxygenase, blockade of neutrophil chemo taxis and mast cell activation, and impairment of nuclear factor κB activation (NF κB) in immune cells 3 . Moreover, studies in mice revealed that 5 ASA based drugs augment peroxisome proliferator activated receptor γ (PPARγ) expression and promote PPARγ translocation from the cytoplasm to the nucleus where they result in activation of peroxisome proliferator hormone response element driven genes to suppress colitis activity 6,7 .In addition to 5 ASAs, corticosteroids (systemically or topically delivered) have been used for remission induction in ulcerative colitis 2 . Although cortico steroids favour induction of remission in both ulcer ative colitis and Crohn's disease, they are not suitable for mainten ance of remission in IBD 1,2 . Mechanistically, gluco corticoids bind to a specific cytosolic receptor fol lowed by translocation of the complex to the nucleus to either activate or repress gene transcription (via bind ing to DNA corticosteroid response elements) 8,9 . Additionally, the glucocorticoid-receptor complex can inactivate pro inflammatory transcription factors such as NF κB and activator protein 1 (AP1) via proteinprotein inter actions, thereby preventing their activation of inflammatory mediators (for example, leukotrienes and cytokines such as IL 1 and IL 6). REVIEWS© 2 0 1 7 M a c m i l l a n P u b l i s h e r s L i m i t e d , p a r t o f S p r i n g e r N a t u r e . A l l r i g h t s r e s e r v e d .

show abstract

Section: T Cellmentioning

confidence: 99%

Current and emerging therapeutic targets for IBD

Neurath

2017

Nat Rev Gastroenterol Hepatol

485

376

View full text Add to dashboard Cite

show abstract

“…[14][15][16] Bacterial genomic DNA is thus suspected to play a key role in Figure 4 BLG-specific IgG2a detection in sera of mice treated with LL(pLIG:BLG1) or LL(pLIG1). Mice were force fed 5 days consecutively with LL(pLIG:BLG1) and LL(pLIG) and again 3 weeks after the last gavage.…”

Section: Discussionmentioning

confidence: 99%

In vivo transfer of plasmid from food-grade transiting lactococci to murine epithelial cells

Pothelune

Ah‐Leung

et al. 2008

Gene Ther

View full text Add to dashboard Cite

We recently demonstrated that noninvasive food-grade Lactococcus lactis (L. lactis) can deliver eukaryotic expression plasmid in mammalian cells in vitro. Here, we evaluated, in vivo, whether a eukaryotic expression plasmid carried by lactococci can translocate to the epithelial cells of the intestinal membrane. The strain LL(pLIG:BLG1) carrying one plasmid containing a eukaryotic expression cassette encoding b-lactoglobulin (BLG), a major allergen of cow's milk, was orally administered by gavage to mice. BLG cDNA was detected in the epithelial membrane of the small intestine of 40% of the mice and BLG was produced in 53% of the mice. Oral administration of LL(pLIG:BLG1) induced a low and transitory Th1-type immune response counteracting a Th2 response in case of further sensitization. We demonstrated for the first time the transfer of a functional plasmid to the epithelial membrane of the small intestine in mice by noninvasive food-grade lactococci.

show abstract

“…113 These effects were shown to be due to probiotic DNA, which when given orally could inhibit disease activity and improve histologic scores to a similar extent as whole live bacteria. In addition, a single subcutaneous (s.c.) administration of probiotic DNA protected against TNBS-induced colitis and spontaneous colitis in IL-10 −/− mice.…”

Section: Probiotics In Infl Ammatory Diseases Of the Bowelmentioning

confidence: 99%

“…181 In addition, DNA has been shown to mediate a variety of immunomodulatory effects of certain probiotic strains both in vitro and in vivo. 48,113,177 Note that ISS-DNA sequences have been identifi ed in a variety of probiotic strains, including LGG, 182 Lactobacillus delbrueckii ssp. bulgaricus NIAI B6, 183 Lactobacillus gasseri OLL2716, 184 and B. longum BB536.…”

Section: Identifi Cation Of Active Probiotics Components and Receptormentioning

confidence: 99%

Probiotics and immunity

et al. 2009

View full text Add to dashboard Cite

Probiotics are defi ned as live microorganisms that, when administered in adequate amounts, confer a health benefi t on the host, including the gastrointestinal tract. While this benefi cial effect was originally thought to stem from improvements in the intestinal microbial balance, there is now substantial evidence that probiotics can also provide benefi ts by modulating immune functions. In animal models, probiotic supplementation is able to provide protection from spontaneous and chemically induced colitis by downregulating infl ammatory cytokines or inducing regulatory mechanisms in a strain-specifi c manner. In animal models of allergen sensitization and murine models of asthma and allergic rhinitis, orally administered probiotics can straindependently decrease allergen-specifi c IgE production, in part by modulating systemic cytokine production. Certain probiotics have been shown to decrease airway hyperresponsiveness and infl ammation by inducing regulatory mechanisms. Promising results have been obtained with probiotics in the treatment of human infl ammatory diseases of the intestine and in the prevention and treatment of atopic eczema in neonates and infants. However, the fi ndings are too variable to allow fi rm conclusions as to the effectiveness of specifi c probiotics in these conditions.

show abstract

Toll-like receptor 9 signaling mediates the anti-inflammatory effects of probiotics in murine experimental colitis

Cited by 768 publications

References 23 publications

Current and emerging therapeutic targets for IBD

Current and emerging therapeutic targets for IBD

In vivo transfer of plasmid from food-grade transiting lactococci to murine epithelial cells

Probiotics and immunity

Contact Info

Product

Resources

About