Enhanced macrophage antitumor effects of protein A in combination with IFN-γ

1999 ◽  
Vol 22 (3) ◽  
pp. 267-273
Author(s):  
Suhkneung Pyo ◽  
Dong-Kwon Rhee
Keyword(s):  
Protein A ◽  
Antitumor Effects ◽  
Ifn Γ

scholarly journals CD4 T Cell Antigens from Staphylococcus aureus Newman Strain Identified following Immunization with Heat-Killed Bacteria

2012 ◽  
Vol 19 (4) ◽  
pp. 477-489 ◽  
Author(s):  
Paulraj K. Lawrence ◽  
Bachra Rokbi ◽  
Nadège Arnaud-Barbe ◽  
Eric L. Sutten ◽  
Junzo Norimine ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
T Cell ◽  
Reverse Genetics ◽  
Vaccine Development ◽  
Protein A ◽  
Cd4 T Cell ◽  
Content Type ◽  
Intramammary Infections ◽  
T Cell Antigens ◽  
Ifn Γ

ABSTRACTStaphylococcus aureusis a commensal bacterium associated with the skin and mucosal surfaces of humans and animals that can also cause chronic infection. The emergence of antibiotic-resistant strains such as methicillin-resistantS. aureus(MRSA) and strains causing chronic intramammary infections (IMI) in cows results in severe human and livestock infections. Conventional approaches to vaccine development have yielded only a few noneffective vaccines against MRSA or IMI strains, so there is a need for improved vaccine development. CD4 T lymphocytes are required for promoting gamma interferon (IFN-γ) mediated immunoglobulin isotype switching in B lymphocytes to produce high-affinity IgG antibodies and IFN-γ-mediated phagocyte activation for an effective resolution of bacterial infection. However, the lack of known CD4 T cell antigens fromS. aureushas made it difficult to design effective vaccines. The goal of this study was to identifyS. aureusproteins recognized by immune CD4 T cells. Using a reverse genetics approach, 43 antigens were selected from theS. aureusNewman strain. These included lipoproteins, proteases, transcription regulators, an alkaline shock protein, conserved-domain proteins, hemolysins, fibrinogen-binding protein, staphylokinase, exotoxin, enterotoxin, sortase, and protein A. Screening of expressed proteins for recall T cell responses in outbred, immune calves identified 13 proteins that share over 80% sequence identity among MRSA or IMI strains. These may be useful for inclusion in a broadly protective multiantigen vaccine against MRSA or IMI.

scholarly journals Synergistic antitumor effects of celecoxib with 5-fluorouracil depend on IFN-γ

2007 ◽  
Vol 121 (4) ◽  
pp. 878-883 ◽  
Author(s):  
Takanobu Irie ◽  
Masahiko Tsujii ◽  
Shingo Tsuji ◽  
Toshiyuki Yoshio ◽  
Shuji Ishii ◽  
...  
Keyword(s):  
Antitumor Effects ◽  
Ifn Γ

Interleukin-2 enhances the response of natural killer cells to interleukin-12 through up-regulation of the interleukin-12 receptor and STAT4

Blood ◽  
2000 ◽  
Vol 95 (10) ◽  
pp. 3183-3190 ◽  
Author(s):  
Kathy S. Wang ◽  
David A. Frank ◽  
Jerome Ritz
Keyword(s):  
T Lymphocytes ◽  
Nk Cells ◽  
Natural Killer ◽  
Critical Role ◽  
Interleukin 2 ◽  
Interleukin 12 ◽  
Target Cells ◽  
Functional Responses ◽  
Antitumor Effects ◽  
Ifn Γ

Interleukin (IL)-12 plays a critical role in modulating the activities of natural killer (NK) cells and T lymphocytes. In animal models, IL-12 has potent antitumor effects that are likely mediated by its ability to enhance the cytotoxic activity of NK cells and cytotoxic T lymphocytes, and to induce the production of interferon (IFN)-γ by NK and T cells. In addition to IL-12, NK cells are responsive to IL-2, and may mediate some of the antitumor effects of IL-2. In this study, we examine the interaction between IL-2 and the signaling events induced by IL-12 in NK cells. We find that IL-2 not only up-regulates the expression of IL-12Rβ1 and IL-12Rβ2, it also plays an important role in up-regulating and maintaining the expression of STAT4, a critical STAT protein involved in IL-12 signaling in NK cells. In contrast to the effects of IL-2 alone, expression of IL-12 receptors and STAT4 are unaffected or decreased by IL-12 or the combination of IL-2 and IL-12. Through expression of high levels of IL-12 receptors and STAT4, IL-2–primed NK cells show enhanced functional responses to IL-12 as measured by IFN-γ production and the killing of target cells. NK cells from cancer patients who received low-dose IL-2 treatment also exhibited increased expression of IL-12 receptor chains, suggesting that IL-2 may enhance the response to IL-12 in vivo. These findings provide a molecular framework to understand the interaction between IL-2 and IL-12 in NK cells, and suggest strategies for improving the effectiveness of these cytokines in the immunotherapy of cancer.

scholarly journals In Vivo Bioluminescence Visualization of Antitumor Effects by Human MUC1 Vaccination

2007 ◽  
Vol 6 (5) ◽  
pp. 7290.2007.00027 ◽  
Author(s):  
Yong Hyun Jeon ◽  
Yun Choi ◽  
Hyun Joo Kim ◽  
Joo Hyun Kang ◽  
Chul Woo Kim ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Growth Inhibition ◽  
Optical Imaging ◽  
Interferon Γ ◽  
Tumor Growth Inhibition ◽  
Imaging Method ◽  
Antitumor Effects ◽  
Human Muc1 ◽  
Ifn Γ

Recently, the use of a cancer deoxyribonucleic acid (DNA) vaccine encoding tumor-associated antigens has emerged as an immunotherapeutic strategy. In this study, we monitored tumor growth inhibition by pcDNA3-hMUC1 immunization in mice using optical imaging. To determine the anti-hMUC1-associated immune response generated by pcDNA3.1 or pcDNA3-hMUC1, we determined the concentration of interferon-γ (IFN-γ) protein and CD8+IFN-γ cell numbers among lymphocytes from the draining lymph nodes of mice immunized with pcDNA3.1 or pcDNA3-hMUC1. After subcutaneously injecting CT26/hMUC1-F luc into mice immunized with pcDNA3-hMUC1, we monitored in vivo tumor growth inhibition using an optical imaging method. The concentration of IFN-γ protein in pcDNA3-hMUC1 was higher than that of the pcDNA3.1 group (2.7 ⩽ 0.08 ng/mL and 1.6 ± 0.07 ng/mL, respectively, p < .001. The number of hMUC1-associated CD8+IFN-γ cells in pcDNA3-hMUC1-immunized animals was 30-fold higher than in the pcDNA3.1 group. Bioluminescent images showed tumor growth inhibition in pcDNA3-hMUC1 immunized animals up to 25 days after immunization. A good correlation ( r2 = .9076: pcDNA3/hMUC1 group; r2 = .7428: pcDNA3.1 group) was observed between bioluminescence signals and tumor weights in two mice in each group. We conclude that optical bioluminescent imaging offers a useful means of monitoring the antitumor effects of cancer DNA immunization in living animals.

scholarly journals The Significance of KL-6 as Prognosis Monitoring Biomarker in Patients With Severe COVID-19 From Stabilized Stage Toward Convalescence

2021 ◽  
Author(s):  
Long He ◽  
Liu Lu ◽  
Ming Zong ◽  
Huang Zhou ◽  
Lan Wang ◽  
...  
Keyword(s):  
Lung Injury ◽  
Protein A ◽  
Alveolar Epithelium ◽  
Surfactant Protein ◽  
Surfactant Protein A ◽  
Monocyte Count ◽  
Type Ii ◽  
Tnf Α ◽  
Ifn Γ ◽  
Blood Routine

Abstract Background: This study aims to identify some biomarkers for monitoring the recovery of lung injury in severe COVID-19 patients from stabilized stage toward convalescence.Methods: We enrolled participants who diagnosed with severe COVID-19 (n = 28) and health volunteers (n = 25) from Taikang Tongji (Wuhan) Hospital. The patients were in a stabilized stage and had a course of 48.1±12.8 days. We followed these patients for 90 days. The blood routine, cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p70, IL-17A, TNF-α, IFN-α, IFN-γ), type II alveolar epithelium injury indicators (Surfactant protein A (SP-A), Krebs von den Lungen-6 (KL-6)) and chest CT were tested on the 1, 30, 60, and 90 days after enrollment. Results: In stabilized stage, the parameters of blood routine and some cytokines (IL-1β, IL-2, IL-4, IL-12p70, TNF-α) had bounced back to normal (p>0.05). Some cytokines (IL-5, IL-6, IL-10, IL-17A, IFN-α, IFN-γ) and type II alveolar epithelium injury indicators (SP-A and KL-6) were still higher than normal (p<0.05). During the stabilized stage to convalescence, in spite of the variation of monocyte count, monocyte/lymphocyte ratio, IL-5, IL-10, IL-12p70, IL-17A, IFN-γ, IFN-α, SP-A and KL-6 were downward trend (p<0.05), only KL-6 level (p<0.05) could simultaneously reflect the lung injury volume which be measured by CT. Conclusions: Our preliminary data indicated that KL-6 could be an effective prognostic biomarker for monitoring the recovery of lung function in patients with severe COVID-19 from stabilized stage toward convalescence.

Phenyl N-Tert-Butylnitrone (PBN) Protects Syngeneic Marrow Transplant Recipients from the Lethal Cytokine Syndrome Occurring after Agonistic CD40 Antibody Administration.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2128-2128
Author(s):  
William R. Drobyski ◽  
Nadine Halligan ◽  
Richard Komorowski ◽  
Brent Logan ◽  
William J. Murphy ◽  
...  
Keyword(s):  
Free Radical ◽  
Organ Damage ◽  
Marrow Transplant ◽  
Antitumor Effects ◽  
Free Radical Production ◽  
Radical Production ◽  
Gut Toxicity ◽  
Significant Difference ◽  
Ifn Γ ◽  
Agonistic Cd40 Antibody

Abstract Administration of agonistic monoclonal antibodies or recombinant cytokines is a potential approach to enhance antitumor immunity in bone marrow transplant (BMT) recipients, but is complicated by toxicity due to proinflammatory cytokine-mediated vital organ damage. Inflammatory cytokines are known to induce free radical production which we hypothesized might be the proximate cause of toxicity in this setting. Phenyl-tert-butylnitrone (PBN) is a spin trap inhibitor, that has been used in electron paramagnetic resonance (EPR) studies to trap free radicals so they can be visualized by EPR spectroscopy. To test whether PBN could mitigate cytokine-mediated organ damage, we employed a murine syngeneic transplant model in which administration of agonistic CD40 antibody to mice early post BMT results in lethality due to production of high levels of cytokines such as IL-12 and IFN-γ, leading to fatal gut toxicity. Lethally irradiated C57BL/6J (B6) mice were transplanted with B6 BM and then treated with either IgG or anti-CD40 antibody (7 μg) on days 1–4 post-BMT. Cohorts of anti-CD40-antibody-treated mice were then administered either DMSO or PBN (50 mg/kg BID) on days 0–5 post-BMT. Administration of PBN completely protected BMT recipients from anti-CD40 antibody-induced mortality (0% survival CD40/DMSO versus 100% survival CD40/PBN). This was attributable to a significant reduction in gut toxicity as determined using a pathological scoring system. To examine the mechanism by which mice were protected, cytokine and nitrate/nitrite levels were measured to determine whether PBN inhibited production of proinflammatory mediators. Administration of anti-CD40 antibody resulted in a significant increase in IL-12, IFN-γ,TNF-α, and nitrate/nitrite levels compared to IgG/PBN-treated control mice. However, there was no significant difference in serum measurements of these cytokines in CD40/PBN compared to CD40/DMSO-treated animals. These data demonstrated that the protective effects of PBN were not attributable to a reduction in cytokine mediators and suggested that the action of PBN occurred downstream of these inflammatory cytokine signaling pathways, through inhibition of free radical production. Cytokines, such as IL-12 and IFN-γ, are also important downstream mediators of the antitumor effects induced by agonistic CD40 antibody. Therefore to directly test whether PBN compromised these antitumor effects, B6 mice were intravenously administered 107 EL4 cells and then treated on days 3-6 with either rat IgG or anti-CD40 antibody. Since EL4 cells do not express CD40, tumor regression mediated by anti-CD40 antibody is attributable to augmentation of host immunity and has been shown to dependent upon IFN-γ. B6 mice were challenged with a lethal dose EL4 tumor cells and then treated with IgG or agonistic CD40 antibody (500 μg/day) in the presence or absence of PBN. IgG-treated control mice all died within 20 days. In contrast, CD40/DMSO and CD40/PBN-treated mice all survived >80 days after tumor challenge indicating that PBN did not compromise antitumor effects. We conclude that PBN administration may represent a novel approach for reduction of toxicity without compromise of antitumor effects resulting from administration of therapeutic antibodies in BMT recipients.

scholarly journals Grape Seed Extract Activates Th1 Cells In Vitro

2002 ◽  
Vol 9 (2) ◽  
pp. 470-476 ◽  
Author(s):  
Narayanan Nair ◽  
Supriya Mahajan ◽  
Ram Chawda ◽  
Chithan Kandaswami ◽  
Thomas C. Shanahan ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Mononuclear Cells ◽  
Biological Activities ◽  
Grape Seed Extract ◽  
Grape Seed ◽  
Seed Extract ◽  
Antitumor Effects ◽  
Peripheral Blood Mononuclear ◽  
Diverse Range ◽  
Ifn Γ

ABSTRACT Although flavonoids manifest a diverse range of biological activities, including antitumor and antiviral effects, the molecular mechanisms underlying these activities await elucidation. We hypothesize that the flavonoid constituents of a proprietary grape seed extract (GSE) that contains procyandins exert significant antiviral and antitumor effects, by inducing production of the Th1-derived cytokine gamma interferon (IFN-γ) by peripheral blood mononuclear cells) from healthy donors. Our results show that GSE significantly induced the transcription of IFN-γ mRNA as demonstrated by reverse transcription-PCR but had no effect on the Th2-derived cytokine interleukin-6. The enhancing effect of GSE on IFN-γ expression was further supported by a concomitant increase in the number of cells with intracytoplasmic IFN-γ as well as the synthesis and secretion of IFN-γ. Our results demonstrate that the potentially beneficial immunostimulatory effects of GSE may be mediated through the induction of IFN-γ.

scholarly journals IFN-γ Mediates the Antitumor Effects of Radiation Therapy in a Murine Colon Tumor

2013 ◽  
Vol 182 (6) ◽  
pp. 2345-2354 ◽  
Author(s):  
Scott A. Gerber ◽  
Abigail L. Sedlacek ◽  
Kyle R. Cron ◽  
Shawn P. Murphy ◽  
John G. Frelinger ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Colon Tumor ◽  
Antitumor Effects ◽  
Ifn Γ ◽  
Effects Of Radiation ◽  
Murine Colon

scholarly journals TNF-α and the IFN-γ-inducible protein 10 (IP-10/CXCL-10) delivered by parvoviral vectors act in synergy to induce antitumor effects in mouse glioblastoma

2008 ◽  
Vol 16 (2) ◽  
pp. 149-160 ◽  
Author(s):  
M Enderlin ◽  
E V Kleinmann ◽  
S Struyf ◽  
C Buracchi ◽  
A Vecchi ◽  
...  
Keyword(s):  
Antitumor Effects ◽  
Tnf Α ◽  
Ifn Γ ◽  
Inducible Protein
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