scholarly journals Identification of the Primary Structure of Selenium-Containing Polysaccharides Selectively Inhibiting T-Cell Proliferation

Molecules ◽  
2021 ◽  
Vol 26 (17) ◽  
pp. 5404
Author(s):  
Marzenna Klimaszewska ◽  
Sabina Górska ◽  
Grzegorz Łapienis ◽  
Beata Kaleta ◽  
Sandra Górska ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Primary Structure ◽  
Lentinula Edodes ◽  
Inhibitory Effect ◽  
Biologically Active ◽  
T Cell Proliferation ◽  
Immunosuppressive Activity ◽  
High Molar Mass ◽  
Mycelial Culture ◽  
Polysaccharide Fraction

We previously described the biosynthesis, isolation, and immunosuppressive activity of the selenium-containing polysaccharide fraction isolated from the mycelial culture of Lentinula edodes. Structural studies have shown that the fraction was a protein-containing mixture of high molar mass polysaccharides α- and β-glucans. However, which of the components of the complex fraction is responsible for the immunosuppressive activity non-typical for polysaccharides of fungal origin has not been explained. In the current study, we defined four-polysaccharide components of the Se-containing polysaccharide fraction determined their primary structure and examined the effect on T- and B-cell proliferation. The isolated Se-polysaccharides, α-1,4-glucan (Mw 2.25 × 106 g/mol), unbranched β-1,6-d-glucan, unbranched β-1,3-d-glucan and β-1,3-branched β-1,6-d-glucan (Mw 1.10 × 105 g/mol), are not typical as components of the cell wall of L. edodes. All are biologically active, but the inhibitory effect of the isolated polysaccharides on lymphocyte proliferation was weaker, though more selective than that of the crude fraction.

scholarly journals Immunosuppressive activity of bovine seminal RNase on T-cell proliferation

1990 ◽  
Vol 190 (1) ◽  
pp. 145-148 ◽  
Author(s):  
Maurizio TAMBURRINI ◽  
Giuseppe SCALA ◽  
Cinzia VERDE ◽  
Maria Rosaria RUOCCO ◽  
Augusto PARENTE ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
T Cell ◽  
T Cell Proliferation ◽  
Immunosuppressive Activity

scholarly journals Bioactivity-Guided Isolation and Identification of New and Immunosuppressive Monoterpenoid Indole Alkaloids from Rauvolfia yunnanensis Tsiang

Molecules ◽  
2019 ◽  
Vol 24 (24) ◽  
pp. 4574 ◽  
Author(s):  
Li-Mei Li ◽  
Shun-Dong Shi ◽  
Yang Liu ◽  
Qiang Zou
Keyword(s):  
Cell Proliferation ◽  
T Cell ◽  
Indole Alkaloids ◽  
T Cell Proliferation ◽  
Ionization Mass ◽  
Immunosuppressive Activity ◽  
Isolation And Identification ◽  
Monoterpenoid Indole Alkaloids ◽  
Total Alkaloids ◽  
Ic50 Values

Three new 11-hydroxyburnamine (1) and rauvoyunnanines A–B (2–3), and fourteen known (4–17) monoterpenoid indole alkaloids were isolated from the total alkaloids extract of Rauvolfia yunnanensis, which exhibited promising immunosuppressive activity on T cell proliferation in preliminary screening. Their structures were determined by analysis of high-resolution electrospray ionization mass (HRESIMS), ultraviolet (UV) and nuclear magnetic resonance (NMR) data, and by comparison with the literature. All the alkaloids were evaluated for inhibitory activity on T cell proliferation. Among them, one new compound (1) and reserpine (6) exhibited moderate immunosuppressive activity, with IC50 values of 5.9 μM and 5.0 μM, respectively.

Evidence for an opioid inhibitory effect on T cell proliferation

1993 ◽  
Vol 44 (1) ◽  
pp. 43-48 ◽  
Author(s):  
B. Manfredi ◽  
P. Sacerdote ◽  
M. Bianchi ◽  
L. Locatelli ◽  
J. Veljic-Radulovic ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
T Cell ◽  
Inhibitory Effect ◽  
T Cell Proliferation

scholarly journals Biological and physical approaches on the role of piplartine (piperlongumine) in cancer

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Tiago Henrique ◽  
Caroline de F. Zanon ◽  
Ana P. Girol ◽  
Ana Carolina Buzzo Stefanini ◽  
Nayara S. de A. Contessoto ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Therapeutic Potential ◽  
Inhibitory Effect ◽  
Physicochemical Analysis ◽  
Biologically Active ◽  
Migration And Invasion ◽  
Annexin A1 ◽  
Anti Inflammatory ◽  
Mimic Peptide

AbstractChronic inflammation provides a favorable microenvironment for tumorigenesis, which opens opportunities for targeting cancer development and progression. Piplartine (PL) is a biologically active alkaloid from long peppers that exhibits anti-inflammatory and antitumor activity. In the present study, we investigated the physical and chemical interactions of PL with anti-inflammatory compounds and their effects on cell proliferation and migration and on the gene expression of inflammatory mediators. Molecular docking data and physicochemical analysis suggested that PL shows potential interactions with a peptide of annexin A1 (ANXA1), an endogenous anti-inflammatory mediator with therapeutic potential in cancer. Treatment of neoplastic cells with PL alone or with annexin A1 mimic peptide reduced cell proliferation and viability and modulated the expression of MCP-1 chemokine, IL-8 cytokine and genes involved in inflammatory processes. The results also suggested an inhibitory effect of PL on tubulin expression. In addition, PL apparently had no influence on cell migration and invasion at the concentration tested. Considering the role of inflammation in the context of promoting tumor initiation, the present study shows the potential of piplartine as a therapeutic immunomodulator for cancer prevention and progression.

Membrane-Associated Proteinase 3 on Granulocytes and Myeloid Leukemia Mediates Reversible Inhibition of T Cell Proliferation

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1916-1916
Author(s):  
Tian-Hui Yang ◽  
Karen Clise-Dwyer ◽  
Gheath Alatrash ◽  
Kathryn Ruisaard ◽  
Shoudan Liang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Myeloid Leukemia ◽  
Inhibitory Effect ◽  
T Cell Proliferation ◽  
Proteinase 3 ◽  
Healthy Donors ◽  
Membrane Bound

Abstract Abstract 1916 Proteinase 3 (P3), a serine protease constitutively expressed in primary granules and on the membrane of some resting granulocytes, is the target of T cell-mediated autoimmunity in Wegener's granulomatosis (WG) and of anti-leukemia immunity mediated by PR1 (VLQELNVTV)-specific cytotoxic T lymphocytes (PR1-CTL). We have shown that soluble P3 is increased by 5-fold in sera from acute myeloid leukemia (AML) patients compared to healthy controls, and soluble P3 mediates enzyme-independent inhibition of T-cell proliferation. Moreover, tumor-associated neutrophils (TANs) are associated with a poor prognosis in a number of cancers including renal cell carcinoma and lung cancer, and P3 is also over-expressed in a variety of AML and chronic myeloid leukemia (CML). Therefore, we hypothesized that membrane-bound P3 (mP3) may similarly regulate adaptive immunity by suppressing T-cell proliferation. To study this, T cells from healthy donors were labeled with the membrane dye CFSE and stimulated with anti-CD3 and anti-CD28 in the presence or absence of mP3-expressing PMNs for five days. The percentage of proliferating cells was determined by flow cytometry. Proliferation of autologous CD8+ and CD4+ T cells was significantly inhibited by 75% and 72%, respectively, when PMNs were co-incubated with lymphocytes at a ratio of 3:1, and by > 90% at 5:1. This cell contact-dependent inhibitory effect was limited to PMN since PBMCs added to lymphocytes in place of PMNs at 5:1 had no effect on T cell proliferation. To determine whether the inhibitory effect was specifically mediated by mP3, we FAC-sorted CD177+PMNs and CD177−PMNs to obtain highly purified (>98%) mP3+ and mP3− PMNs, respectively, because CD177 and mP3 are co-expressed on same subset of resting PMNs. At a ratio of 3:1 (CD177+PMNs or CD177−PMNs to lymphocytes), mP3+PMNs mediated > 75% growth inhibition of both CD8+ and CD4+ T cells compared to < 55% inhibition by mP3−PMNs (p<0.05). Furthermore, the inhibitory effect of mP3+PMNs on T cell proliferation was blocked (< 10% inhibition of proliferation) by anti-P3 but not by isotype control mAb. The inhibitory effect of mP3 was enzyme-independent because Elafin or α1-anti-trypsin did not affect inhibition by mP3+PMNs. In addition, mP3-mediated inhibition was fully reversible as T cells proliferated normally with anti-CD3/anti-CD28 stimulation after PMNs were removed from co-culture. Similarly, mP3+AML blasts inhibited autologous CD8+ and CD4+ T cell proliferation by 50% and 30%, respectively, at a 2:1 ratio of AML blasts: lymphocytes. Interestingly, bone marrow myeloid derived suppressor cells (MDSC) from leukemia patients express significantly higher mP3 (79.4±5.23% (mean±SEM, n=7)), compared to 22.4±11.55% mP3 on MDSC from healthy donors (p= 0.0007, n=3). Taken together, these data support an important new function of membrane-bound P3 on innate immune cells and leukemia in controlling adaptive T cell immunity. These findings suggest a novel mechanism whereby neutrophils could promote tumor growth in vivo through contact-mediated suppression of tumor-infiltrating lymphocytes by mP3 or by soluble P3 secreted by activated TANs in cancer and myeloid leukemia. Thus, targeting P3 with anti-P3 antibodies may be explored as a novel therapeutic strategy for leukemia and other cancers. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Interaction of leukocyte integrins with ligand is necessary but not sufficient for function.

1992 ◽  
Vol 116 (6) ◽  
pp. 1527-1535 ◽  
Author(s):  
I Dransfield ◽  
C Cabañas ◽  
J Barrett ◽  
N Hogg
Keyword(s):  
Cell Proliferation ◽  
T Cell ◽  
Killer Cell ◽  
Inhibitory Effect ◽  
T Cell Proliferation ◽  
Lymphocyte Function ◽  
Receptor Ligand ◽  
Leukocyte Integrins ◽  
Cell Assays ◽  
Ligand Interactions

The leukocyte integrins (CD11/CD18 or beta 2-type integrins) are expressed exclusively on leukocytes and participate in many adhesion-dependent functions (Arnaout, M.A. 1990. Blood. 75:1037-1050; Springer, T. A. 1990. Nature. (Lond.) 346:425-434; Dustin, M. L., and T. S. Springer. 1991. Annu. Rev. Immunol. 9:27-66). The avidity of leukocyte integrin binding to their ligands or counter-receptors is dependent upon response to intracellular signals (Wright, S. D., and B. C. Meyer. 1986. J. Immunol. 136:1759-1764; Dustin, M. A., and T. S. Springer. 1989. Nature (Lond.). 341:619-624). We have investigated the effects of a novel mAb (mAb 24) which defines a leukocyte integrin alpha subunit epitope that is Mg(2+)-dependent and may be used as a "reporter" of the activation state of these receptors (Dransfield, I., and N. Hogg. 1989. EMBO (Eur. Mol. Biol. Organ) J. 8:3759-3765; Dransfield, I., A.-M. Buckle, and N. Hogg. 1990. Immunol. Rev. 114:29-44; Dransfield, I., C. Cabañas, A. Craig, and N. Hogg. 1992. J. Cell Biol.) Data is presented to show that this mAb inhibits monocyte-dependent, antigen-specific T cell proliferation and IL-2-activated natural killer cell assays which are both dependent on lymphocyte function-associated antigen-1 (LFA-1), and complement receptor type 3 (CR3)-mediated neutrophil chemotaxis to f-Met-Leu-Phe. This inhibitory effect is not caused by the prevention of receptor/ligand binding because LFA-1/ICAM-1, LFA-1/ICAM-2,3 and CR3/iC3b interactions are, under activating conditions, promoted rather than blocked by mAb 24. As it does not interfere with mitogen-stimulated T cell proliferation, it is unlikely that mAb 24 transduces a "negative" or antiproliferative signal to the T cells to which it is bound. Using a model system of transient activation of LFA-1, we have found that mAb 24 prevents "deadhesion" of receptor/ligand pairs, possibly locking leukocyte integrins in an "active" conformation. It is speculated that inhibition of leukocyte integrin function by this mAb reflects the necessity for dynamic leukocyte integrin/ligand interactions.

scholarly journals Specific Inhibitory Action of Anisodamine against a Staphylococcal Superantigenic Toxin, Toxic Shock Syndrome Toxin 1 (TSST-1), Leading to Down-Regulation of Cytokine Production and Blocking of TSST-1 Toxicity in Mice

2005 ◽  
Vol 12 (3) ◽  
pp. 399-408 ◽  
Author(s):  
Saori Nakagawa ◽  
Koji Kushiya ◽  
Ikue Taneike ◽  
Ken'ichi Imanishi ◽  
Takehiko Uchiyama ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
T Cell ◽  
Proinflammatory Cytokines ◽  
Toxic Shock Syndrome ◽  
Inhibitory Effect ◽  
Herbal Extract ◽  
T Cell Proliferation ◽  
Toxic Shock ◽  
Toxic Shock Syndrome Toxin

ABSTRACT Toxic shock syndrome toxin 1 (TSST-1), produced by Staphylococcus aureus (including methicillin-resistant S. aureus), is a superantigenic toxin responsible for toxic shock syndrome as well as neonatal TSS-like exanthematous disease. TSST-1 exhibits its deleterious effects by leading to the abnormal proliferation of, e.g., Vβ2+ T cells and overproduction of proinflammatory cytokines. In the present study we examined the inhibitory effect of a Chinese herbal extract, anisodamine, on TSST-1 using human peripheral blood mononuclear cells (PBMCs). Anisodamine inhibited the production of proinflammatory cytokines better than interleukin-10 (an anti-inflammatory cytokine). The inhibitory effect of anisodamine was greater than that of any tropane alkaloid examined. Anisodamine acted directly on both monocytes and T cells in human PBMCs, and the effect was confirmed at the transcriptional level. Inhibition of NF-κB activation was also demonstrated. In contrast, no significant inhibition of Vβ2+ T-cell proliferation was observed. In mice injected with TSST-1, anisodamine treatment significantly decreased serum proinflammatory cytokine levels and prevented TSST-1-induced death. These results suggest that anisodamine specifically acts against the production of cytokines (inflammatory cytokines in particular) and not against Vβ2+ T-cell proliferation and that anisodamine may have a beneficial effect on TSST-1-associated disease.

scholarly journals A procedure for in vitro evaluation of the immunosuppressive effect of mesenchymal stem cells on activated T cell proliferation

2020 ◽  
Author(s):  
Catalina Marinescu ◽  
Bogdan Preda ◽  
Alexandrina Burlacu
Keyword(s):  
Cell Proliferation ◽  
T Cell ◽  
Inhibitory Effect ◽  
Immunosuppressive Effect ◽  
T Cell Proliferation ◽  
Immunomodulatory Capacity ◽  
Activated T Cell ◽  
Dose Dependent

Abstract Background: Mesenchymal stem/stromal cells (MSC) represent adult cells with multipotent capacity. Besides their capacity to differentiate into multiple lineages in vitro and in vivo, increasing evidence points towards the immunomodulatory capacity of these cells, as an important feature for their therapeutic power. Although not included in the minimal criteria established by the International Society for Cellular Therapy as a defining MSC attribute, demonstration of the immunomodulatory capacity of MSC can be useful for the characterization of these cells before being considered MSC. Here we present a simple and reliable protocol by which the immunosuppressive effect of MSC can be evaluated in vitro. It is based on the measuring of the proliferation of activated T cells cultured in direct contact with irradiated MSC.Results: Our results showed that MSC have a dose-dependent inhibitory effect on activated T cell proliferation, which can be quantified as a percentage of maximum proliferation. Our data shows that batch-to-batch variability can be determined within one or multiple experiments, by extracting the area under curve of T cell proliferation plotted against the absolute number of MSC in co-culture.Conclusions: The validation of the immunomodulatory capacity of MSC could be added to the characterization of the cells before being used in various MSC-based approaches to treat immunological diseases. Our results showed that MSC have a dose-dependent inhibitory effect on activated T cell proliferation. The immunosuppressive properties of MSC vary between batches, but not between different passages of the same batch.

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