scholarly journals Mechanisms of Action of Probiotics

2019 ◽  
Vol 10 (suppl_1) ◽  
pp. S49-S66 ◽  
Author(s):  
Julio Plaza-Diaz ◽  
Francisco Javier Ruiz-Ojeda ◽  
Mercedes Gil-Campos ◽  
Angel Gil
Keyword(s):  
Molecular Mechanisms ◽  
T Regulatory Cells ◽  
Transforming Growth Factor ◽  
Interleukin 10 ◽  
Mechanisms Of Action ◽  
Short Chain ◽  
Probiotic Properties ◽  
Peripheral Tissues ◽  
Nonalcoholic Fatty Liver ◽  
Mucin Production

ABSTRACT Probiotics are living microorganisms that confer health benefits to the host when administered in adequate amounts; however, dead bacteria and their components can also exhibit probiotic properties. Bifidobacterium and strains of lactic acid bacteria are the most widely used bacteria that exhibit probiotic properties and are included in many functional foods and dietary supplements. Probiotics have been shown to prevent and ameliorate the course of digestive disorders such as acute, nosocomial, and antibiotic-associated diarrhea; allergic disorders such as atopic dermatitis (eczema) and allergic rhinitis in infants; and Clostridium difficile–associated diarrhea and some inflammatory bowel disorders in adults. In addition, probiotics may be of interest as coadjuvants in the treatment of metabolic disorders, including obesity, metabolic syndrome, nonalcoholic fatty liver disease, and type 2 diabetes. However, the mechanisms of action of probiotics, which are diverse, heterogeneous, and strain specific, have received little attention. Thus, the aim of the present work was to review the main mechanisms of action of probiotics, including colonization and normalization of perturbed intestinal microbial communities in children and adults; competitive exclusion of pathogens and bacteriocin production; modulation of fecal enzymatic activities associated with the metabolization of biliary salts and inactivation of carcinogens and other xenobiotics; production of short-chain and branched-chain fatty acids, which, in turn, have wide effects not only in the intestine but also in peripheral tissues via interactions with short-chain fatty acid receptors, modulating mainly tissue insulin sensitivity; cell adhesion and mucin production; modulation of the immune system, which results mainly in the differentiation of T-regulatory cells and upregulation of anti-inflammatory cytokines and growth factors, i.e., interleukin-10 and transforming growth factor; and interaction with the brain-gut axis by regulation of endocrine and neurologic functions. Further research to elucidate the precise molecular mechanisms of action of probiotics is warranted.

Indoleamine 2,3-dioxgenase-transfected mesenchymal stem cells suppress heart allograft rejection by increasing the production and activity of dendritic cells and regulatory T cells

2019 ◽  
Vol 68 (3) ◽  
pp. 728-737 ◽  
Author(s):  
Ji-Gang He ◽  
Bei-Bei Li ◽  
Liang Zhou ◽  
Dan Yan ◽  
Qiao-Li Xie ◽  
...  
Keyword(s):  
Stem Cells ◽  
T Cells ◽  
Mesenchymal Stem Cells ◽  
Dendritic Cells ◽  
Transforming Growth Factor Beta ◽  
Allograft Rejection ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Interleukin 10 ◽  
Heart Allograft

Expression of indoleamine 2,3-dioxygenase (IDO) in mesenchymal stem cells (MSC) is thought to contribute to MSC-mediated immunosuppression. A lentiviral-based transgenic system was used to generate bone marrow stem cells (BMSC) which stably expressed IDO (IDO-BMSCs). Coculture of IDO-BMSCs with dendritic cells (DC) or T cells was used to evaluate the immunomodulatory effect of IDO-BMSCs. A heterotopic heart transplant model in rats was used to evaluate allograft rejection after IDO-BMSC treatment. Mechanisms of IDO-BMSC-mediated immunosuppression were investigated by evaluating levels of proinflammatory and anti-inflammatory cytokines, and production of Tregs. A significant decrease in DC marker-positive cells and a significant increase in Tregs were observed in IDO-BMSC cocultured. Treatment of transplanted rats with IDO-BMSCs was associated with significantly prolonged graft survival. Compared with the control groups, transplanted animals treated with IDO-BMSCs had a (1) significantly higher ejection fraction and fractional shortening, (2) significantly lower expression of CD86, CD80, and MHCII, and significantly higher expression in CD274, and Tregs, and (3) significantly higher levels of interleukin-10 (IL-10), transforming growth factor beta-1 (TGF-β1), TGF-β2, and TGF-β3, and significantly lower levels of IL-2 and interferon gamma. Our results expand our understanding of the molecular mechanisms underlying suppression of heart allograft rejection via IDO-expressing BMSCs.

scholarly journals MerTK-mediated regulation of myelin phagocytosis by macrophages generated from patients with MS

2017 ◽  
Vol 4 (6) ◽  
pp. e402 ◽  
Author(s):  
Luke M. Healy ◽  
Jeong Ho Jang ◽  
So-Yoon Won ◽  
Yun Hsuan Lin ◽  
Hanane Touil ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Messenger Rna ◽  
Healthy Donor ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Interleukin 10 ◽  
Tyrosine Kinase Receptor ◽  
Blood Monocytes ◽  
Myelin Phagocytosis ◽  
Donor Cells

Objective:To document functional differences between monocyte-derived macrophages (MDMs) of patients with MS and the ability of age/sex-matched healthy donor cells to phagocytose human myelin and to investigate the molecular mechanisms that underlie this.Methods:MDMs were derived from peripheral blood monocytes of 25 untreated patients with relapsing-remitting MS and secondary progressive MS and age/sex-matched healthy controls (HCs). Phagocytosis was assessed by flow cytometry using fluorescently labeled human myelin. Quantification of messenger RNA and protein expression of Tyro3, Axl, and MerTK family molecules was determined by quantitative PCR, Western blotting, and flow cytometry.Results:Cells of patients with MS display a reduced ability to phagocytose human myelin but not red blood cells as compared to matched HCs. These cells express significantly lower levels of the phagocytic tyrosine kinase receptor, MerTK, and its natural ligand, growth arrest-specific 6, independently of the activation state of the cells. Increased expression of interleukin 10 following myelin uptake by healthy donor cells is lost in MDMs of patients with MS; this effect is mediated through the MerTK pathway. Treatment of MS cells with transforming growth factor β (TGFβ) restored both phagocytosis and expression deficits.Conclusions:We describe a molecular mechanism that underlies a defect in myelin phagocytosis by macrophages generated from patients with MS. This abnormality involves decreased expression of MerTK and its ligands and can be rescued by treatment with TGFβ.

scholarly journals Differentiation of type 1 T regulatory cells (Tr1) by tolerogenic DC-10 requires the IL-10–dependent ILT4/HLA-G pathway

Blood ◽  
2010 ◽  
Vol 116 (6) ◽  
pp. 935-944 ◽  
Author(s):  
Silvia Gregori ◽  
Daniela Tomasoni ◽  
Valentina Pacciani ◽  
Miriam Scirpoli ◽  
Manuela Battaglia ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
T Regulatory Cells ◽  
Interleukin 10 ◽  
Regulatory Cells ◽  
Hla Dr ◽  
Human Dendritic Cells ◽  
Tr1 Cells

Abstract Type 1 T regulatory (Tr1) cells suppress immune responses in vivo and in vitro and play a key role in maintaining tolerance to self- and non–self-antigens. Interleukin-10 (IL-10) is the crucial driving factor for Tr1 cell differentiation, but the molecular mechanisms underlying this induction remain unknown. We identified and characterized a subset of IL-10–producing human dendritic cells (DCs), termed DC-10, which are present in vivo and can be induced in vitro in the presence of IL-10. DC-10 are CD14+, CD16+, CD11c+, CD11b+, HLA-DR+, CD83+, CD1a−, CD1c−, express the Ig-like transcripts (ILTs) ILT2, ILT3, ILT4, and HLA-G antigen, display high levels of CD40 and CD86, and up-regulate CD80 after differentiation in vitro. DC-10 isolated from peripheral blood or generated in vitro are potent inducers of antigen-specific IL-10–producing Tr1 cells. Induction of Tr1 cells by DC-10 is IL-10–dependent and requires the ILT4/HLA-G signaling pathway. Our data indicate that DC-10 represents a novel subset of tolerogenic DCs, which secrete high levels of IL-10, express ILT4 and HLA-G, and have the specific function to induce Tr1 cells.

scholarly journals The Impact of the Tumor Microenvironment on Macrophage Polarization in Cancer Metastatic Progression

2021 ◽  
Vol 22 (12) ◽  
pp. 6560
Author(s):  
Huogang Wang ◽  
Mingo M. H. Yung ◽  
Hextan Y. S. Ngan ◽  
Karen K. L. Chan ◽  
David W. Chan
Keyword(s):  
Tumor Microenvironment ◽  
Solid Tumors ◽  
Tumor Metastasis ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Macrophage Polarization ◽  
Interleukin 10 ◽  
The Body ◽  
Metastatic Progression ◽  
The Impact

Rather than primary solid tumors, metastasis is one of the hallmarks of most cancer deaths. Metastasis is a multistage event in which cancer cells escape from the primary tumor survive in the circulation and disseminate to distant sites. According to Stephen Paget's “Seed and Soil” hypothesis, metastatic capacity is determined not only by the internal oncogenic driving force but also by the external environment of tumor cells. Throughout the body, macrophages are required for maintaining tissue homeostasis, even in the tumor milieu. To fulfill these multiple functions, macrophages are polarized from the inflammation status (M1-like) to anti-inflammation status (M2-like) to maintain the balance between inflammation and regeneration. However, tumor cell-enforced tumor-associated macrophages (TAMs) (a high M2/M1 ratio status) are associated with poor prognosis for most solid tumors, such as ovarian cancer. In fact, clinical evidence has verified that TAMs, representing up to 50% of the tumor mass, exert both protumor and immunosuppressive effects in promoting tumor metastasis through secretion of interleukin 10 (IL10), transforming growth factor β (TGFβ), and VEGF, expression of PD-1 and consumption of arginine to inhibit T cell anti-tumor function. However, the underlying molecular mechanisms by which the tumor microenvironment favors reprogramming of macrophages to TAMs to establish a premetastatic niche remain controversial. In this review, we examine the latest investigations of TAMs during tumor development, the microenvironmental factors involved in macrophage polarization, and the mechanisms of TAM-mediated tumor metastasis. We hope to dissect the critical roles of TAMs in tumor metastasis, and the potential applications of TAM-targeted therapeutic strategies in cancer treatment are discussed.

Active suppression of allogeneic proliferative responses by dendritic cells after induction of long-term allograft survival by CTLA4Ig

Blood ◽  
2003 ◽  
Vol 101 (8) ◽  
pp. 3325-3333 ◽  
Author(s):  
Cécile Guillot ◽  
Séverine Ménoret ◽  
Carole Guillonneau ◽  
Cécile Braudeau ◽  
Maria G. Castro ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Combined Treatment ◽  
Interleukin 10 ◽  
No Production ◽  
Allograft Survival

Abstract Costimulatory blockade using cytotoxic T lymphocyte–associated antigen 4 immunoglobulin (CTLA4Ig) efficiently down-regulates immune responses in animal models and is currently used in autoimmune and transplantation clinical trials, but the precise cellular and molecular mechanisms involved remain unclear. Rats that received allogeneic heart transplants and were treated with adenoviruses coding for CTLA4Ig show long-term allograft survival. The immune mechanisms regulating induction of long-term allograft acceptance were analyzed in splenocytes using mixed leukocyte reactions (MLRs). MLRs of splenocytes but not purified T cells from CTLA4Ig-treated rats showed higher than 75% inhibition compared with controls. Splenocytes from CTLA4Ig-treated rats inhibited proliferation of naive and allogeneically primed splenocytes or T cells. MLR suppression was dependent on soluble secreted product(s). Production of soluble inhibitory product(s) was triggered by a donor antigen-specific stimulation and inhibited proliferation in an antigen-nonspecific manner. CTLA4Ig levels in the culture supernatant were undetectable and neither interleukin-10 (IL-10), transforming growth factor β1 (TGFβ1), IL-4, nor IL-13 were responsible for suppression of MLRs. Inhibition of nitrous oxide (NO) production or addition of IL-2 could not restore proliferation independently, but the combined treatment synergistically induced proliferation comparable with controls. Stimulation of APCs using tumor necrosis factor (TNF)–related activation-induced cytokine (TRANCE) or CD40L and addition of IL-2 normalized MLRs of CTLA4Ig-treated splenocytes. Finally, dendritic cells (DCs), but not T cells, from CTLA4Ig-treated rats inhibited naive MLRs. Altogether, these results provide evidence that after in vivo CTLA4Ig treatment, splenocytes, and in particular DCs, can inhibit alloantigen-induced proliferative responses through secretion of inhibitory products, thus promoting alloantigen-specific tolerance in vivo.

scholarly journals The correlation between lncRNAs and Helicobacter pylori in gastric cancer

2019 ◽  
Vol 77 (9) ◽  
Author(s):  
Narges Dastmalchi ◽  
Seyed Mahdi Banan Khojasteh ◽  
Mirsaed Miri Nargesi ◽  
Reza Safaralizadeh
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Molecular Mechanisms ◽  
Gastrointestinal Diseases ◽  
Mechanisms Of Action ◽  
Molecular Pathways ◽  
Gastric Diseases ◽  
Non Coding Rnas ◽  
H Pylori ◽  
The Relationship

ABSTRACT Helicobacter pylori infection performs a key role in gastric tumorigenesis. Long non-coding RNAs (lncRNAs) have demonstrated a great potential to be regarded as effective malignancy biomarkers for various gastrointestinal diseases including gastric cancer (GC). The present review highlights the relationship between lncRNAs and H. pylori in GC. Several studies have examined not only the involvement of lncRNAs in H. pylori-associated GC progression but also their molecular mechanisms of action. Among the pertinent studies, some have addressed the effects of H. pylori infection on modulatory networks of lncRNAs, while others have evaluated the effects of changes in the expression level of lncRNAs in H. pylori-associated gastric diseases, especially GC. The relationship between lncRNAs and H. pylori was found to be modulated by various molecular pathways.

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