Lactobacillus suntoryeus inhibits pro-inflammatory cytokine expression and TLR-4-linked NF-κB activation in experimental colitis

Molecular Medicine Reports

Jiao

et al. 2015

Abstract. Sepsis is one of the leading causes of mortality in severe systemic inflammatory syndrome. The endotoxin-induced inflammatory response has been linked to the development of sepsis. Rhein is a lipophilic anthraquinone isolated from Rheum rhabarbarum (rhubarb), which has a protective effect on intestinal damage in vivo. However, the underlying mechanism responsible for the protective effects of rhein remains to be elucidated. In the present study, mice were exposed to 20 mg/kg lipopolysaccharide (LPS), prior to being treated with either 100 mg/kg rhein or 0.3 mg/kg toll-like receptor 4 (TLR4) signaling inhibitor TAK-242. In the rhein-treated mice, the colon length (cm) was extended and colon injury was attenuated. In addition, treatment with rhein significantly decreased the expression levels of the LPS-induced inflammatory cytokines interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor-α, in both the plasma and colon tissue. However, mice treated with TAK-242 exhibited increased expression levels of IL-10, as determined by ELISA and western blot analysis. In addition, immunohistochemistry and western blot analyses demonstrated that treatment with rhein was able to reduce TLR4 expression and inhibit nuclear factor-κB (NF-κB) phosphorylation in colon tissue. Furthermore, LPS induction was blocked by TAK-242. These results demonstrate that the observed rhein-attenuated inflammatory response during sepsis may be achieved via the TLR4 NF-κB signaling pathway. In conclusion, the results of the present study provide a novel insight into the protective effects of rhein on LPS-induced intestinal inflammation, and demonstrate that rhein may act as a beneficial therapeutic agent in the treatment of sepsis-induced intestinal damage.

Section: Discussionsupporting

confidence: 58%

Rhein inhibits lipopolysaccharide-induced intestinal injury during sepsis by blocking the toll-like receptor 4 nuclear factor-κB pathway

Molecular Medicine Reports

Jiao

et al. 2015

“…These results are in agreement with those of Federico et al [29] , who have found that a symbiotic preparation that contained Lactobacillus paracasei B 20160 restored the serum level and mRNA expression of IL-6, IL-8, and TNF-α in UC patients. Other investigators have found that Lactobacillus HY 7801 blocks tri-nitrobenzenesulfonic-acid-stimulated MPO activity in the intestine, as well as the expression of IL-1β, and TNF-α [30] . A prominent feature of mucosal histology in patients with active IBD is infiltration by neutrophilic granulocytes [31] .…”

Section: B Amentioning

confidence: 93%

“…The rat-specific primers (sense and antisense primers) for TNF-α and β-actin were 5′-CAT-GATCCGAGATGTGGAACTGGC-3′ and 5′-CTG-GCTCAGCCACTCCAGC-3′ (TNF-α, 315 bp) and 5′-ATGGATGACGATATCGCTG-3′ and 5′-ATGAG-GTAGTCTGTCAGGT-3′ (β-actin, 568 bp), respectively. Amplification was performed in 30 …”

Section: Detection Of Colonic Of Nf-κb P65mentioning

confidence: 99%

Effect of probiotics on pro-inflammatory cytokines and NF-κB activation in ulcerative colitis

Hegazy

El-Bedewy²

2010

WJG

214

121

AIM:To demonstrate the therapeutic effect of probiotics in patients with ulcerative colitis (UC), and their effect on inflammatory mediators and nuclear factor (NF)-κB activation in these patients. METHODS:Thirty patients with mild to moderate UC were randomly classified into two groups: sulfasalazine group, who received sulfasalazine 2400 mg/d; and probiotic group, who received sulfasalazine 2400 mg/d with probiotic. The patients were investigated before and after 8 wk of treatment with probiotic (Lactobacillus delbruekii and Lactobacillus fermentum ). Colonic activity of myeloperoxidase (MPO) was assayed with UV spectrophotometry, the colonic content of interleukin (IL)-6 was determined by enzyme-linked immunosorbent assay (ELISA), fecal calprotectin was determined by ELISA, and expression of NF-κB p65 and tumor necrosis factor (TNF)-α proteins in colonic tissue was identified by immunohistochemistry and reverse transcription polymerase chain reaction, respectively. RESULTS:At the start of the study, colonic mucosal injury and inflammation were demonstrated in UC patients by hematoxylin and eosin staining, and an increase in colonic MPO activity, fecal calprotectin, and expression of colonic TNF-α and NF-κB p65 proteins. The use of probiotic for 8 wk significantly ameliorated the inflammation by decreasing the colonic concentration of IL-6, expression of TNF-α and NF-κB p65, leukocyte recruitment, as demonstrated by a decrease in colonic MPO activity, and the level of fecal calprotectin compared to sulfasalazine group and the control group (P < 0.05). CONCLUSION:Oral supplementation with probiotics could be helpful in maintaining remission and preventing relapse of UC.

“…Recent studies indicated that Lactobacillus suntoryeus, a gut commensal, blocks inflammatory mediators (Cox2, TNF-␣, IL-1, and IL-6) through suppression of TLR4-mediated NF-B activation in mice with TNBS-induced colitis (19). Lubbad et al (23) have reported that amelioration of TNBS-induce colitis by curcumin is mediated through TLR4-linked NF-B inhibition.…”

mentioning

confidence: 99%

Paeoniflorin abrogates DSS-induced colitis via a TLR4-dependent pathway

Dou

American Journal of Physiology-Gastrointestinal and Liver Physi

et al. 2014

110

Paeonia lactiflora Pall is one of the most well-known herbs in China, Korea, and Japan for more than 1,200 years. Paeoniflorin, the major bioactive component of peony root, has recently been reported to have anticolitic activity. However, the underlying molecular mechanism is unclear. The present study was to explore the possible mechanism of paeoniflorin in attenuating dextran sulfate sodium (DSS)-induced colitis. Pre- and coadministration of paeoniflorin significantly reduced the severity of colitis and resulted in downregulation of several inflammatory parameters in the colon, including the activity of myeloperoxidase (MPO), the levels of TNF-α and IL-6, and the mRNA expression of proinflammatory mediators (MCP-1, Cox2, IFN-γ, TNF-α, IL-6, and IL-17). The decline in the activation of NF-κB p65, ERK, JNK, and p38 MAPK correlated with a decrease in mucosal Toll-like receptor 4 (TLR4) but not TLR2 or TLR5 expression. In accordance with the in vivo results, paeoniflorin downregulated TLR4 expression, blocked nuclear translocation of NF-κB p65, and reduced the production of IL-6 in LPS-stimulated mouse macrophage RAW264.7 cells. Transient transfection assay performed in LPS-stimulated human colon cancer HT-29 cells indicated that paeoniflorin inhibits NF-κB transcriptional activity in a dose-dependent manner. TLR4 knockdown and overexpression experiments demonstrated a requirement for TLR4 in paeoniflorin-mediated downregulation of inflammatory cytokines. Thus, for the first time, the present study indicates that paeoniflorin abrogates DSS-induced colitis via decreasing the expression of TLR4 and suppressing the activation of NF-κB and MAPK pathways.