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Anti-inflammatory effects of Lactococcus lactis NCDO 2118 during the remission period of chemically induced colitis.

Luerce TD, Gomes-Santos AC, Rocha CS, Moreira TG, Cruz DN, Lemos L, Sousa AL, Pereira VB, de Azevedo M, Moraes K, Cara DC, LeBlanc JG, Azevedo V, Faria AM, Miyoshi A - Gut Pathog (2014)

Bottom Line: Only one strain, L. lactis NCDO 2118, was able to reduce IL-1β-induced IL-8 secretion in Caco-2 cells, suggesting a potential anti-inflammatory effect.This protective effect was not attributable to changes in secretory IgA (sIgA); however, NCDO 2118 administration was associated with an early increase in IL-6 production and sustained IL-10 production in colonic tissue.Here, we identified a new probiotic strain with a potential role in the treatment of IBD, and we elucidated some of the mechanisms underlying its anti-inflammatory effect.

View Article: PubMed Central - HTML - PubMed

Affiliation: Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627 - 31270-901 Belo Horizonte, MG, Brazil.

ABSTRACT

Background: Many probiotic bacteria have been described as promising tools for the treatment and prevention of inflammatory bowel diseases (IBDs). Most of these bacteria are lactic acid bacteria, which are part of the healthy human microbiota. However, little is known about the effects of transient bacteria present in normal diets, including Lactococcus lactis.

Methods: In the present study, we analysed the immunomodulatory effects of three L. lactis strains in vitro using intestinal epithelial cells. L. lactis NCDO 2118 was administered for 4 days to C57BL/6 mice during the remission period of colitis induced by dextran sodium sulphate (DSS).

Results: Only one strain, L. lactis NCDO 2118, was able to reduce IL-1β-induced IL-8 secretion in Caco-2 cells, suggesting a potential anti-inflammatory effect. Oral treatment using L. lactis NCDO 2118 resulted in a milder form of recurrent colitis than that observed in control diseased mice. This protective effect was not attributable to changes in secretory IgA (sIgA); however, NCDO 2118 administration was associated with an early increase in IL-6 production and sustained IL-10 production in colonic tissue. Mice fed L. lactis NCDO 2118 had an increased number of regulatory CD4(+) T cells (Tregs) bearing surface TGF-β in its latent form (Latency-associated peptide-LAP) in the mesenteric lymph nodes and spleen.

Conclusions: Here, we identified a new probiotic strain with a potential role in the treatment of IBD, and we elucidated some of the mechanisms underlying its anti-inflammatory effect.

No MeSH data available.


Related in: MedlinePlus

Effect of L. lactis NCDO 2118 on T cells and tolerogenic dendritic cells. The numbers of activated T cells, regulatory T cells and tolerogenic dendritic cells in chemically induced colitis were determined in the mesenteric lymph nodes (mLNs) and spleen; the cells were stained at day 21. (A) Number of CD4 + CD69+ T cells. (B) CD4 + CD25 + CD45RBlow T cells. (C) CD4 + CD25 + LAP + T cells. (D) CD11c + CD11b-CD103+ cells. Bars are the mean of 5 mice/group, and the data are representative of two independent experiments; ANOVA, Tukey post-test. **, p < 0.01, ***, p < 0.001.
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Figure 6: Effect of L. lactis NCDO 2118 on T cells and tolerogenic dendritic cells. The numbers of activated T cells, regulatory T cells and tolerogenic dendritic cells in chemically induced colitis were determined in the mesenteric lymph nodes (mLNs) and spleen; the cells were stained at day 21. (A) Number of CD4 + CD69+ T cells. (B) CD4 + CD25 + CD45RBlow T cells. (C) CD4 + CD25 + LAP + T cells. (D) CD11c + CD11b-CD103+ cells. Bars are the mean of 5 mice/group, and the data are representative of two independent experiments; ANOVA, Tukey post-test. **, p < 0.01, ***, p < 0.001.

Mentions: Because the intestinal inflammation in DSS-induced colitis is triggered by microbial antigens, induction of oral tolerance to microbiota could be one of the potential mechanisms by which L. lactis NCDO 2118 stimulates the immune system. Because oral tolerance is maintained mainly by Treg cells [23], we analysed the changes in CD4+CD25+CD45RBlow and CD4+CD25+LAP+ T cells in the mesenteric lymph nodes and spleens of mice. L. lactis NCDO 2118 did not alter the numbers of activated T cells in mesenteric lymph nodes. However, this treatment enhanced the number of activated T cells (CD69+) in the spleen (Figure 6A), suggesting that some L. lactis products are able to activate T cells in vivo. The population of CD4+CD25+CD45RBlow regulatory T cells was not affected by DSS or DSS-NCDO2118 treatment (Figure 6B). The same result was observed for CD4+Foxp3+ Tregs (data not shown). Nevertheless, the levels of CD4+CD25+LAP+ regulatory T cells were increased in the mesenteric lymph nodes and spleens of NCDO 2118-treated mice.


Anti-inflammatory effects of Lactococcus lactis NCDO 2118 during the remission period of chemically induced colitis.

Luerce TD, Gomes-Santos AC, Rocha CS, Moreira TG, Cruz DN, Lemos L, Sousa AL, Pereira VB, de Azevedo M, Moraes K, Cara DC, LeBlanc JG, Azevedo V, Faria AM, Miyoshi A - Gut Pathog (2014)

Effect of L. lactis NCDO 2118 on T cells and tolerogenic dendritic cells. The numbers of activated T cells, regulatory T cells and tolerogenic dendritic cells in chemically induced colitis were determined in the mesenteric lymph nodes (mLNs) and spleen; the cells were stained at day 21. (A) Number of CD4 + CD69+ T cells. (B) CD4 + CD25 + CD45RBlow T cells. (C) CD4 + CD25 + LAP + T cells. (D) CD11c + CD11b-CD103+ cells. Bars are the mean of 5 mice/group, and the data are representative of two independent experiments; ANOVA, Tukey post-test. **, p < 0.01, ***, p < 0.001.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4126083&req=5

Figure 6: Effect of L. lactis NCDO 2118 on T cells and tolerogenic dendritic cells. The numbers of activated T cells, regulatory T cells and tolerogenic dendritic cells in chemically induced colitis were determined in the mesenteric lymph nodes (mLNs) and spleen; the cells were stained at day 21. (A) Number of CD4 + CD69+ T cells. (B) CD4 + CD25 + CD45RBlow T cells. (C) CD4 + CD25 + LAP + T cells. (D) CD11c + CD11b-CD103+ cells. Bars are the mean of 5 mice/group, and the data are representative of two independent experiments; ANOVA, Tukey post-test. **, p < 0.01, ***, p < 0.001.
Mentions: Because the intestinal inflammation in DSS-induced colitis is triggered by microbial antigens, induction of oral tolerance to microbiota could be one of the potential mechanisms by which L. lactis NCDO 2118 stimulates the immune system. Because oral tolerance is maintained mainly by Treg cells [23], we analysed the changes in CD4+CD25+CD45RBlow and CD4+CD25+LAP+ T cells in the mesenteric lymph nodes and spleens of mice. L. lactis NCDO 2118 did not alter the numbers of activated T cells in mesenteric lymph nodes. However, this treatment enhanced the number of activated T cells (CD69+) in the spleen (Figure 6A), suggesting that some L. lactis products are able to activate T cells in vivo. The population of CD4+CD25+CD45RBlow regulatory T cells was not affected by DSS or DSS-NCDO2118 treatment (Figure 6B). The same result was observed for CD4+Foxp3+ Tregs (data not shown). Nevertheless, the levels of CD4+CD25+LAP+ regulatory T cells were increased in the mesenteric lymph nodes and spleens of NCDO 2118-treated mice.

Bottom Line: Only one strain, L. lactis NCDO 2118, was able to reduce IL-1β-induced IL-8 secretion in Caco-2 cells, suggesting a potential anti-inflammatory effect.This protective effect was not attributable to changes in secretory IgA (sIgA); however, NCDO 2118 administration was associated with an early increase in IL-6 production and sustained IL-10 production in colonic tissue.Here, we identified a new probiotic strain with a potential role in the treatment of IBD, and we elucidated some of the mechanisms underlying its anti-inflammatory effect.

View Article: PubMed Central - HTML - PubMed

Affiliation: Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627 - 31270-901 Belo Horizonte, MG, Brazil.

ABSTRACT

Background: Many probiotic bacteria have been described as promising tools for the treatment and prevention of inflammatory bowel diseases (IBDs). Most of these bacteria are lactic acid bacteria, which are part of the healthy human microbiota. However, little is known about the effects of transient bacteria present in normal diets, including Lactococcus lactis.

Methods: In the present study, we analysed the immunomodulatory effects of three L. lactis strains in vitro using intestinal epithelial cells. L. lactis NCDO 2118 was administered for 4 days to C57BL/6 mice during the remission period of colitis induced by dextran sodium sulphate (DSS).

Results: Only one strain, L. lactis NCDO 2118, was able to reduce IL-1β-induced IL-8 secretion in Caco-2 cells, suggesting a potential anti-inflammatory effect. Oral treatment using L. lactis NCDO 2118 resulted in a milder form of recurrent colitis than that observed in control diseased mice. This protective effect was not attributable to changes in secretory IgA (sIgA); however, NCDO 2118 administration was associated with an early increase in IL-6 production and sustained IL-10 production in colonic tissue. Mice fed L. lactis NCDO 2118 had an increased number of regulatory CD4(+) T cells (Tregs) bearing surface TGF-β in its latent form (Latency-associated peptide-LAP) in the mesenteric lymph nodes and spleen.

Conclusions: Here, we identified a new probiotic strain with a potential role in the treatment of IBD, and we elucidated some of the mechanisms underlying its anti-inflammatory effect.

No MeSH data available.


Related in: MedlinePlus