Immunobiotic Lactobacillus jensenii Modulates the Toll-Like Receptor 4-Induced Inflammatory Response via Negative Regulation in Porcine Antigen-Presenting Cells

Villena, Julio; Suzuki, Rie; Fujie, Hiromi; Chiba, Eriko; Takahashi, Takuya; Tomosada, Yohsuke; Shimazu, Tomoyuki; Aso, Hisashi; Ohwada, Shyuichi; Suda, Yoshihito; Ikegami, Shuji; Itoh, Hiroyuki; Alvarez, Susana; Saito, Tadao; Kitazawa, Haruki

doi:10.1128/cvi.00199-12

Cited by 75 publications

(130 citation statements)

References 44 publications

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“…In addition, we previously demonstrated that A20, Bcl-3 and Tollip mRNA levels can be upregulated by immunobiotics in a TLR2-dependent manner [10, 12]. In the present work, we showed that the three negative regulators of TLRs were upregulated by the MCC-117 and ATCC15705 strains, with B. breve MCC-117 being the most effective strain for the induction of Tollip and Bcl-3.…”

Section: Discussionsupporting

confidence: 64%

<i>Bifidobacterium breve</i> MCC-117 Induces Tolerance in Porcine Intestinal Epithelial Cells: Study of the Mechanisms Involved in the Immunoregulatory Effect

Murata

Tomosada

Villena

et al. 2014

Bioscience of Microbiota, Food and Health

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Bifidobacterium breve MCC-117 is able to significantly reduce the expression of inflammatory cytokines in porcine intestinal epithelial (PIE) cells and to improve IL-10 levels in CD4+CD25high Foxp3+ lymphocytes in response to heat-stable enterotoxigenic Escherichia coli (ETEC) pathogen-associated molecular patterns (PAMPs), while the immunoregulatory effect of B. adolescentis ATCC15705 was significantly lower than that observed for the MCC-117 strain. Considering the different capacities of the two bifidobacterium strains to activate toll-like receptor (TLR)-2 and their differential immunoregulatory activities in PIE and immune cells, we hypothesized that comparative studies with both strains could provide important information regarding the molecular mechanism(s) involved in the anti-inflammatory activity of bifidobacteria. In this work, we demonstrated that the anti-inflammatory effect of B. breve MCC-117 was achieved by a complex interaction of multiple negative regulators of TLRs as well as inhibition of multiple signaling pathways. We showed that B. breve MCC-117 reduced heat-stable ETEC PAMP-induced NF-κB, p38 MAPK and PI3 K activation and expression of pro-inflammatory cytokines in PIE cells. In addition, we demonstrated that B. breve MCC-117 may activate TLR2 synergistically and cooperatively with one or more other pattern recognition receptors (PRRs), and that interactions may result in a coordinated sum of signals that induce the upregulation of A20, Bcl-3, Tollip and SIGIRR. Upregulation of these negative regulators could have an important physiological impact on maintaining or reestablishing homeostatic TLR signals in PIE cells. Therefore, in the present study, we gained insight into the molecular mechanisms involved in the immunoregulatory effect of B. breve MCC-117.

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Section: Discussionsupporting

confidence: 64%

<i>Bifidobacterium breve</i> MCC-117 Induces Tolerance in Porcine Intestinal Epithelial Cells: Study of the Mechanisms Involved in the Immunoregulatory Effect

Murata

Tomosada

Villena

et al. 2014

Bioscience of Microbiota, Food and Health

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“…More recently, Finamore et al (2014) signaling in Caco-2/TC7 cells through modulation of the negative regulators Tollip and IRAK-M and, that this effect was dependent on TLR2 signaling. Our previous studies in PIE cells and porcine immune cells also revealed that TLR2 plays an important role in the immunoregulatory activity of immunobiotic bacteria (Shimazu et al, 2012;Tomosada et al, 2013;Villena et al, 2012;Murata et al, 2014). Our studies of the anti-inflammatory activity of L. jensenii TL2937 in PIE cells showed that TLR2 have an important role in the immunoregulatory capacities of this strain.…”

Section: Discussionmentioning

confidence: 50%

The toll-like receptor family protein RP105/MD1 complex is involved in the immunoregulatory effect of exopolysaccharides from Lactobacillus plantarum N14

Murofushi

Villena

Morie

et al. 2015

Molecular Immunology

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“…Another study showed that SIGIRR protects from hydrocarbon oil-induced lupus [13]. There is much difference in the role of SIGIRR in SLE patients and animal models [14,15]. Taken together, the results of these studies demonstrate that SIGIRR is a key molecule in the control of chronic autoimmune diseases, including SLE.…”

Section: Introductionmentioning

confidence: 81%

“…Individual disease activity was quantified by using the SLE disease activity index (SLEDAI) score. SLE activity was defined on basis of SLEDAI scores: no or mild activity (SLE-DAI = 0-5), moderate activity (SLEDAI = 6-10), high activity (SLEDAI = [11][12][13][14][15][16][17][18][19], and very high activity (SLEDAI C 20) [19]. The study protocol was approved by the Ethics Committee of Anhui Medical University.…”

Section: Patients and Controlsmentioning

confidence: 99%

The decreased frequency of SIGIRR-positive CD4+ T cells in peripheral blood of patients with SLE and its correlation with disease activity

Wang

Chen

et al. 2014

Mol Biol Rep

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Recently, many studies have shown that Single immunoglobulin interleukin-1 receptor related protein (SIGIRR), a member of the IL-1R family acting as a negative regulator of TLR/IL-1R signaling, affects autoimmune responses in animal model of systemic lupus erythematosus (SLE). However, the role of SIGIRR in the pathogenesis of human SLE has not been widely explored. In this study, we analyzed the frequency of SIGIRR-positive CD4+ T cells in peripheral blood mononuclear cells (PBMCs) of SLE patients and its correlation with disease activity as well as the clinical data. Circulating SIGIRR-positive CD4+ T cells were quantified in 51 SLE patients and 38 healthy controls by using flow cytometer. Results showed that the percentages of SIGIRR-positive CD4+ T cells were decreased in the PBMCs of SLE patients compared with healthy controls (Z = -5.49, P < 0.001). The frequency of SIGIRR-positive CD4 + T cells were also significantly decreased in SLE patients with nephritis than those without nephritis (Z = -3.71, P < 0.001). In addition, there was significant correlation between the percentages of SIGIRR-positive CD4+ T cells and SLEDAI score (r s = -0.74, P < 0.001), 24-hour urine protein (r s = -0.62, P < 0.001), Scr (r s = -0.65, P < 0.001), ESR (r s = -0.60, P < 0.001), C3 (r s = 0.53, P < 0.001) as well as C4 (r s = 0.52, P < 0.001). However, there was no correlation between the proportion of SIGIRR-positive CD4+ T cells and glucocorticoid dose (P = 0.59). In summary, decreased numbers of SIGIRR-positive CD4+ T cells in SLE patients and its correlation with SLEDAI score as well as the clinical data suggest that SIGIRR may be involved in the pathogenesis of SLE.

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Immunobiotic Lactobacillus jensenii Modulates the Toll-Like Receptor 4-Induced Inflammatory Response via Negative Regulation in Porcine Antigen-Presenting Cells

Cited by 75 publications

References 44 publications

<i>Bifidobacterium breve</i> MCC-117 Induces Tolerance in Porcine Intestinal Epithelial Cells: Study of the Mechanisms Involved in the Immunoregulatory Effect

<i>Bifidobacterium breve</i> MCC-117 Induces Tolerance in Porcine Intestinal Epithelial Cells: Study of the Mechanisms Involved in the Immunoregulatory Effect

The toll-like receptor family protein RP105/MD1 complex is involved in the immunoregulatory effect of exopolysaccharides from Lactobacillus plantarum N14

The decreased frequency of SIGIRR-positive CD4+ T cells in peripheral blood of patients with SLE and its correlation with disease activity

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