scholarly journals Oral administration ofLactobacillus acidophilusinduces IL-12 production in spleen cell culture of BALB/c mice bearing transplanted breast tumour

2010 ◽  
Vol 104 (2) ◽  
pp. 227-232 ◽  
Author(s):  
Mohammad Hossein Yazdi ◽  
Mohammad Mehdi Soltan Dallal ◽  
Zuhair Mohammad Hassan ◽  
Marzieh Holakuyee ◽  
Solmaz Agha Amiri ◽  
...  
Keyword(s):  
Immune Responses ◽  
Oral Administration ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Breast Tumour ◽  
Delayed Type Hypersensitivity ◽  
Daily Consumption ◽  
Colony Forming Units ◽  
And Control ◽  
Tumour Transplantation

Lactic acid bacteria can affect the maturation of immune cells and their products not only in the gut but also on the systemic immune organs such as lymph nodes and spleen. In the present work, we studied the effects of oral administration ofLactobacillus acidophiluson the immune responses of BALB/c mice bearing transplanted breast tumour. Two groups of female inbred BALB/c mice, each containing nine mice as test and control, were used. TheL. acidophilusATCC4356 strain was inoculated in DeMan–Rogosa–Sharpe broth and cultivated for 24 h at 37°C. Then, it was collected by centrifugation, and was washed and suspended in PBS. Afterwards, 0·5 ml/d of this suspension, which contained 2·7 × 108 colony forming units/ml of bacteria, was orally administered to the mice by gavage, 14 d before tumour transplantation and 30 d after that with 3-d intervals. Similar to the test mice, the control mice received an equal volume of PBS. The results showed that oral administration ofL. acidophilusincreased the production of IL-12 (P < 0·05) and decreased the level of transforming growth factor β (P = 0·05) in the splenocyte culture. Moreover, the growth rate of tumour in the test mice decreased (P < 0·01), and the results of delayed-type hypersensitivity assay after 48 h were risen (P < 0·05) in comparison with the controls. Results suggest that daily consumption ofL. acidophiluscan improve the production of immunomodulatory cytokine IL-12 in the splenocyte culture, which was stimulated by tumour antigen in BALB/c mice bearing transplanted breast tumour. But further studies are needed to find out some other possible mechanisms of this effect.

scholarly journals Uterine double-conditional inactivation ofSmad2andSmad3in mice causes endometrial dysregulation, infertility, and uterine cancer

2019 ◽  
Vol 116 (9) ◽  
pp. 3873-3882 ◽  
Author(s):  
Maya Kriseman ◽  
Diana Monsivais ◽  
Julio Agno ◽  
Ramya P. Masand ◽  
Chad J. Creighton ◽  
...  
Keyword(s):  
Target Genes ◽  
Transforming Growth Factor ◽  
Uterine Cancer ◽  
Transforming Growth Factor Β ◽  
Cell Cycle Checkpoint ◽  
Conditional Knockout ◽  
Postnatal Life ◽  
Cycle Checkpoint ◽  
Uterine Cancers ◽  
And Control

SMAD2 and SMAD3 are downstream proteins in the transforming growth factor-β (TGF β) signaling pathway that translocate signals from the cell membrane to the nucleus, bind DNA, and control the expression of target genes. While SMAD2/3 have important roles in the ovary, we do not fully understand the roles of SMAD2/3 in the uterus and their implications in the reproductive system. To avoid deleterious effects of global deletion, and given previous data showing redundant function ofSmad2andSmad3, a double-conditional knockout was generated using progesterone receptor-cre (Smad2/3 cKO) mice.Smad2/3cKO mice were infertile due to endometrial hyperproliferation observed as early as 6 weeks of postnatal life. Endometrial hyperplasia worsened with age, and allSmad2/3cKO mice ultimately developed bulky endometrioid-type uterine cancers with 100% mortality by 8 months of age. The phenotype was hormone-dependent and could be prevented with removal of the ovaries at 6 weeks of age but not at 12 weeks. Uterine tumor epithelium was associated with decreased expression of steroid biosynthesis genes, increased expression of inflammatory response genes, and abnormal expression of cell cycle checkpoint genes. Our results indicate the crucial role of SMAD2/3 in maintaining normal endometrial function and confirm the hormone-dependent nature of SMAD2/3 in the uterus. The hyperproliferation of the endometrium affected both implantation and maintenance of pregnancy. Our findings generate a mouse model to study the roles of SMAD2/3 in the uterus and serve to provide insight into the mechanism by which the endometrium can escape the plethora of growth regulatory proteins.

scholarly journals Specificity, versatility, and control of TGF-β family signaling

2019 ◽  
Vol 12 (570) ◽  
pp. eaav5183 ◽  
Author(s):  
Rik Derynck ◽  
Erine H. Budi
Keyword(s):  
Mammalian Cells ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Smad Signaling ◽  
Surface Receptors ◽  
Cell Lineages ◽  
Receptor Complexes ◽  
Signaling Mechanisms ◽  
Dual Specificity ◽  
And Control

Encoded in mammalian cells by 33 genes, the transforming growth factor–β (TGF-β) family of secreted, homodimeric and heterodimeric proteins controls the differentiation of most, if not all, cell lineages and many aspects of cell and tissue physiology in multicellular eukaryotes. Deregulation of TGF-β family signaling leads to developmental anomalies and disease, whereas enhanced TGF-β signaling contributes to cancer and fibrosis. Here, we review the fundamentals of the signaling mechanisms that are initiated upon TGF-β ligand binding to its cell surface receptors and the dependence of the signaling responses on input from and cooperation with other signaling pathways. We discuss how cells exquisitely control the functional presentation and activation of heteromeric receptor complexes of transmembrane, dual-specificity kinases and, thus, define their context-dependent responsiveness to ligands. We also introduce the mechanisms through which proteins called Smads act as intracellular effectors of ligand-induced gene expression responses and show that the specificity and impressive versatility of Smad signaling depend on cross-talk from other pathways. Last, we discuss how non-Smad signaling mechanisms, initiated by distinct ligand-activated receptor complexes, complement Smad signaling and thus contribute to cellular responses.

scholarly journals Transforming Growth Factor-β Signaling in Regulatory T Cells Controls T Helper-17 Cells and Tissue-Specific Immune Responses

Immunity ◽  
2017 ◽  
Vol 46 (4) ◽  
pp. 660-674 ◽  
Author(s):  
Joanne E. Konkel ◽  
Dunfang Zhang ◽  
Peter Zanvit ◽  
Cheryl Chia ◽  
Tamsin Zangarle-Murray ◽  
...  
Keyword(s):  
T Cells ◽  
Growth Factor ◽  
Regulatory T Cells ◽  
Immune Responses ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
T Helper ◽  
T Helper 17 ◽  
T Helper 17 Cells ◽  
Tissue Specific

scholarly journals Orally Administered Mycobacterium vaccae Modulates Expression of Immunoregulatory Molecules in BALB/c Mice with Pulmonary Tuberculosis

2008 ◽  
Vol 15 (11) ◽  
pp. 1730-1736 ◽  
Author(s):  
Rogelio Hernández-Pando ◽  
Diana Aguilar ◽  
Hector Orozco ◽  
Yuriria Cortez ◽  
Laura Rosa Brunet ◽  
...  
Keyword(s):  
T Cells ◽  
Pulmonary Tuberculosis ◽  
Oral Administration ◽  
Subcutaneous Injection ◽  
Transforming Growth Factor ◽  
Cytotoxic T Cells ◽  
Transforming Growth Factor Β ◽  
Interleukin 4 ◽  
High Dose ◽  
Mycobacterium Vaccae

ABSTRACT The environmental saprophyte Mycobacterium vaccae induces a Th1 response and cytotoxic T cells that recognize M. tuberculosis, and by subcutaneous injection, it is therapeutic for pulmonary tuberculosis (TB) induced by high-dose challenge in BALB/c mice. However, M. vaccae also drives regulatory T cells that inhibit Th2 responses, and this is seen in allergy models, not only following subcutaneous injection but also after oral administration. An oral immunotherapeutic for TB would be clinically useful, so we investigated M. vaccae given orally by gavage at 28-day intervals in the TB model. We used two different protocols: starting the oral M. vaccae either 1 day before or 32 days after infection with M. tuberculosis. Throughout the infection (until 120 days), we monitored outcome (CFU), molecules involved in the development of immunoregulation (Foxp3, hemoxygenase 1, idoleamine 2,3-dioxygenase, and transforming growth factor β [TGF-β]), and indicators of cytokine balance (tumor necrosis factor, inducible nitric oxide synthase, interleukin-4 [IL-4], and IL-4δ2; an inhibitory splice variant of IL-4 associated with improved outcome in human TB). Oral M. vaccae had a significant effect on CFU and led to increased expression of Th1 markers and of IL-4δ2, while suppressing IL-4, Foxp3, and TGF-β. When administered 1 day before infection, oral M. vaccae induced a striking peak of expression of hemoxygenase 1. In conclusion, we show novel information about the expression in TB of murine IL-4δ2 and molecules involved in immunoregulation and show that these can be modulated by oral administration of a saprophytic mycobacterium. A clinical trial of oral M. vaccae in extensively drug-resistant TB might be justified.

scholarly journals Checkpoint Inhibitors and Hepatotoxicity

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 101
Author(s):  
Stephen D. H. Malnick ◽  
Ali Abdullah ◽  
Manuela G. Neuman
Keyword(s):  
Immune Responses ◽  
Tumor Cells ◽  
Transforming Growth Factor ◽  
Checkpoint Inhibitors ◽  
Immune Surveillance ◽  
Transforming Growth Factor Β ◽  
Antigenic Modulation ◽  
Growing Cell ◽  
The Individual ◽  
Drug Interventions

Uncontrolled immune response to a pathogen or any protein can lead to tissue damage and autoimmune diseases, that represent aberrant immune responses of the individual to its own cells and/or proteins. The immune checkpoint system is the regulatory mechanism that controls immune responses. Tumor cells escape the immune surveillance mechanism, avoiding immune detection and elimination by activating these checkpoints and suppressing the anti-tumor response, thus allowing formation of tumors. Antigenic modulation facilitates masking and contributes to the escape of tumor cells. In addition, there are growing cell promoters, like transforming growth factor β (TGF-β), contributing to escape mechanisms. Targeting the immunological escape of malignant cells is the basis of immune oncology. Checkpoint inhibitors, cytokines and their antibodies may enhance the immune system’s response to tumors. Currently, immunomodulatory agents have been designed, evaluated in clinical trials and have been approved by both European and United States Drug Agencies. The present review is a reflection of the increasingly important role of the checkpoint inhibitors. Our aim is to review the side effects with the emphasis on hepatic adverse reactions of these novel biological drug interventions.

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