ChemInform Abstract: Structure-Activity Relationships of Quinazoline Derivatives: Dual-Acting Compounds with Inhibitory Activities Toward Both TNF-α Production and T Cell Proliferation.

ChemInform ◽  
2010 ◽  
Vol 32 (23) ◽  
pp. no-no
Author(s):  
Masanori Tobe ◽  
Yoshiaki Isobe ◽  
Hideyuki Tomizawa ◽  
Mitsuhiro Matumoto ◽  
Fumihiro Obara ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
T Cell ◽  
T Cell Proliferation ◽  
Structure Activity Relationships ◽  
Structure Activity ◽  
Tnf Α ◽  
Quinazoline Derivatives ◽  
Inhibitory Activities ◽  
Abstract Structure

scholarly journals The Role of Interleukin-10 (IL-10) in IL-15–Mediated T-Cell Responses

Blood ◽  
1997 ◽  
Vol 90 (11) ◽  
pp. 4513-4521 ◽  
Author(s):  
Dieter Körholz ◽  
Ursula Banning ◽  
Halvard Bönig ◽  
Markus Grewe ◽  
Marion Schneider ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
T Cell ◽  
Interleukin 10 ◽  
T Cell Proliferation ◽  
Cell Production ◽  
Cd25 Expression ◽  
Tnf Α ◽  
Ifn Γ

Abstract Interleukin-15 (IL-15) is a potent T-cell stimulating factor, which has recently been used for pre-clinical in vivo immunotherapy. Here, the IL-15 effect on CD3-stimulated peripheral human T cells was investigated. IL-15 induced a significant T-cell proliferation and upregulated CD25 expression. IL-15 significantly enhanced T-cell production of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and IL-10. Between 10- and 100-fold greater concentrations of IL-15 were necessary to reach a biological effect equivalent to that of IL-2. Blockade of IL-2 binding to the high-affinity IL-2 receptor did not affect the IL-15 effects, suggesting that IL-15 did not act by inducing endogenous IL-2. Exogenously administered IL-10 significantly reduced the IL-15 and IL-2–mediated IFN-γ and TNF-α production, whereas T-cell proliferation and CD25 expression were not affected. The inhibitory effects of exogenously administered IL-10 on T-cell cytokine production appeared indirect, and are likely secondary to decreased IL-12 production by accessory cells. Inhibition of endogenous IL-10 binding to the IL-10 receptor significantly increased IFN-γ and TNF-α release from T cells. These data suggest that endogenous IL-10 can regulate activated T-cell production of IFN-γ and TNF-α via a paracrine negative feedback loop. The observations of this study could be of relevance for the therapeutic use of IL-15 in vivo.

Analysis of T-cell proliferation and cytokine secretion in the individuals exposed to arsenic

2008 ◽  
Vol 27 (5) ◽  
pp. 381-386 ◽  
Author(s):  
R Biswas ◽  
P Ghosh ◽  
N Banerjee ◽  
JK Das ◽  
T Sau ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
T Cell ◽  
Opportunistic Infections ◽  
Arsenic Exposure ◽  
Skin Lesions ◽  
Cytokine Secretion ◽  
T Cell Proliferation ◽  
Internal Organs ◽  
Tnf Α ◽  
Dose Dependent

Over six million people in nine districts of West Bengal, India are exposed to very high levels of arsenic primarily through their drinking water. More than 300,000 people showed arsenic-induced skin lesions in these districts. This is regarded as the greatest arsenic calamity in the world. Chronic arsenicosis causes varied dermatological signs ranging from pigmentation changes, hyperkeratosis to non-melanocytic cancer of skin, and also malignancies in different internal organs. Higher incidences of opportunistic infections are found in the arsenic-exposed individuals, indicating that their immune systems may be impaired somehow. We have thus investigated the effect of arsenic on T-cell proliferation and cytokine secretion in 20 individuals with arsenic-induced skin lesions and compared the results with 18 arsenic-unexposed individuals. A marked dose-dependent suppression of Concanavalin A (Con A) induced T-cell proliferation was observed in the arsenic-exposed individuals compared with the unexposed ( P < 0.001) individuals. This correlated with a significant decrease in the levels of secreted cytokines by the T cells (TNF-α, IFN-γ, IL2, IL10, IL5, and IL4) in the exposed individuals ( P < 0.001). Thus it can be inferred that arsenic exposure can cause immunosuppression in humans.

scholarly journals Multiple Myeloma Cell-Derived Interleukin-32gamma Increases the Immunosuppressive Function of Macrophages By Promoting Indoleamine 2,3-Dioxygenase (IDO) Expression

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3179-3179
Author(s):  
Haimeng Yan ◽  
Donghua He ◽  
Xi Huang ◽  
Zhang En Fan ◽  
He Huang ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Cell Proliferation ◽  
T Cell ◽  
Rna Sequencing ◽  
Cd4 T Cell ◽  
T Cell Proliferation ◽  
Indoleamine 2,3 Dioxygenase ◽  
Tnf Α ◽  
Ifn Γ

Abstract Background: The interaction of multiple myeloma (MM) cells with macrophages (MΦs) in the bone marrow microenvironment contributes to the pathophysiology of MM. In addition to promoting angiogenesis through vasculogenic mimicry, MM-associated MΦs (mMΦs) protect MM cells from spontaneous and chemotherapy-induced apoptosis. mMΦs therefore represent a potential target for myeloma treatment and it is essential to explore the mechanisms underlying normal MΦ polarization to mMΦs. We previously showed that IL-32 is overexpressed in MM patients and is mainly derived from MM cells. The present study was designed to explore the clinical significance of IL-32 in MM and to further elucidate the molecular mechanisms underlying the IL-32-mediated immune function of MΦs. Methods: We examined the expression of IL-32 in bone marrow biopsy samples using immunohistochemistry. Quantitative real-time PCR, western blot analysis and immunofluorescence were applied to measure the expression of IL-32, IDO and proteinase 3 (PR3). We obtained the global transcriptional profile of the IL-32γ-treated MΦs by RNA sequencing (RNA-Seq). Immunoprecipitation (IP) and GST pulldown experiments was applied to confirm the binding affinity of PR3 for IL-32. We created IL-32-knockdown MM cells by transfection of IL-32 shRNA and silenced PR3 expression in MΦs using siRNA targeting PR3. CD4+ T cell proliferation and IL-2, IFN-γ and TNF-α production were measured by flow cytometry. Results: We found that high IL-32 expression in MM patients was associated with advanced clinical stage and high serum β2-microglobulin levels. Several isoforms of IL-32 were detected in MM cells and IL-32γ was the most active subtype. RNA sequencing revealed that IL-32γ significantly induced the production of the immunosuppressive molecule indoleamine 2,3-dioxygenase (IDO) in MΦs and this effect was verified at the protein level. Furthermore, IL-32-knockdown MM cells showed less ability than control MM cells to promote IDO expression. As a binding protein for IL-32, PR3 was universally expressed on the surface of MΦs and knockdown of PR3 or inhibition of the STAT3 and nuclear factor κB (NF-κB) pathways hindered the IL-32γ-mediated stimulation of IDO expression. Finally, IDO-positive IL-32γ-educated MΦs inhibited CD4+ T cell proliferation and IL-2, IFN-γ and TNF-α production in response to activation. Conclusion: Our study showed that MM cell-derived IL-32γ induced IDO production in MΦs through PR3 and the downstream STAT3 and NF-κB pathways, resulting in the suppression of the proliferation and effector function of CD4+ T cells. High IL-32 expression in MM may contribute to an immunosuppressive microenvironment by upregulating IDO production in MΦs and promote MM progression. Disclosures No relevant conflicts of interest to declare.

scholarly journals Two New Xanthone Glycosides from Ventilago Leiocarpa Benth

2008 ◽  
Vol 3 (5) ◽  
pp. 1934578X0800300 ◽  
Author(s):  
Li-Li Wang ◽  
Jian-Ping Zuo ◽  
Lei Ma ◽  
Xia-Chang Wang ◽  
Li-Hong Hu
Keyword(s):  
Cell Proliferation ◽  
T Cell ◽  
B Cell ◽  
T Cell Proliferation ◽  
Inhibitory Activities

Two new xanthone glycosides, 8-hydroxy-3-methyl-6-methoxyxanthone-1- O-β-D-glucopyranosyl-(1→6)-β-D-glucopyranose (1) and 8-hydroxy-3-methyl-6-methoxyxanthone-1- O-α-L-rhamnopyranosyl-(1→6)-β-D-glucopyranose (2), together with two known anthraquinones, 1,8-dihydroxy-3-methylanthraquinone (3) and 1,3,8-trihydroxy-6-methylanthraquinone (4), were isolated from the bark of Ventilago leiocarpa Benth. The structures were determined by various NMR spectroscopic and MS analyses. Compounds 1–4 were tested for their inhibitory activities against T and B cell proliferation, and 2 exhibited moderate inhibitory activities against LPS-induced B cell proliferation and ConA-induced T cell proliferation, with IC50 values of 8.8 and 17.9 μM, respectively.

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