Modification of dendritic cells with interferon-γ-inducible protein-10 gene to enhance vaccine potency

2009 ◽  
Vol 11 (10) ◽  
pp. 889-898 ◽  
Author(s):  
Tae Heung Kang ◽  
Hyun Cheol Bae ◽  
Seok-Ho Kim ◽  
Su Hong Seo ◽  
Sang Wook Son ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Interferon Γ ◽  
Vaccine Potency ◽  
Inducible Protein

Novel heat shock protein Hsp70L1 activates dendritic cells and acts as a Th1 polarizing adjuvant

Blood ◽  
2004 ◽  
Vol 103 (5) ◽  
pp. 1747-1754 ◽  
Author(s):  
Tao Wan ◽  
Xiangyang Zhou ◽  
Guoyou Chen ◽  
Huazhang An ◽  
Taoyong Chen ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Heat Shock ◽  
Cytotoxic T Lymphocyte ◽  
Interferon Γ ◽  
Significant Inhibition ◽  
Effective Vaccine ◽  
Calculated Molecular Weight ◽  
Inducible Protein ◽  
Factor Α ◽  
Shock Proteins

Abstract Heat shock proteins (HSPs) are reported to act as effective adjuvants to elicit anti-tumor and anti-infection immunity. Here, we report that Hsp70-like protein 1 (Hsp70L1), a novel HSP derived from human dendritic cells (DCs), has potent adjuvant effects that polarize responses toward Th1. With a calculated molecular weight of 54.8 kDa, Hsp70L1 is smaller in size than Hsp70 but resembles it both structurally and functionally. Hsp70L1 shares common receptors on DCs with Hsp70 and can interact with DCs, promoting DC maturation and stimulating secretion of the proinflammatory cytokines interleukin 12p70 (IL-12p70), IL-1β, tumor necrosis factor-α (TNF-α), and the chemokines IP-10, macrophage inflammatory protein-1α (MIP-1α), MIP-1β, and normal T cell expressed and secreted (RANTES). The induction of interferon-γ–inducible protein 10 (IP-10) secretion by Hsp70L1 is not shared by Hsp70, and other functional differences include more potent stimulation of DC IL-12p70, CC-chemokine, and CCR7 and CXCR4 expression by Hsp70L1. Immunization of mice with the hybrid peptide Hsp70L1-ovalbumin(OVA)257-264 induces an OVA257-264-specific Th1 response and cytotoxic T lymphocyte (CTL) that results in significant inhibition of E.G7-OVA tumor growth. The ability of Hsp70L1 to activate DCs indicates its potential as a novel adjuvant for use with peptide immunizations; the Hsp70L1 antigen peptide hybrid may serve as a more effective vaccine for the control of cancer and infectious diseases.

scholarly journals Host interferon-γ inducible protein contributes to Brucella survival

2012 ◽  
Vol 2 ◽  
Author(s):  
Jennifer A. Ritchie ◽  
Adam Rupper ◽  
James A. Cardelli ◽  
Bryan H. Bellaire
Keyword(s):  
Interferon Γ ◽  
Inducible Protein

scholarly journals Endogenous CXCL10/Interferon‐γ‐Inducible Protein (IP)‐10 orchestrates myocardial infarct healing

2008 ◽  
Vol 22 (S1) ◽  
Author(s):  
Marcin J. Bujak ◽  
Thorsten Leucker ◽  
Pawel Zymek ◽  
Vikas Veeranna ◽  
Peter Huebener ◽  
...  
Keyword(s):  
Myocardial Infarct ◽  
Interferon Γ ◽  
Infarct Healing ◽  
Inducible Protein

scholarly journals cGAS-mediated stabilization of IFI16 promotes innate signaling during herpes simplex virus infection

2015 ◽  
Vol 112 (14) ◽  
pp. E1773-E1781 ◽  
Author(s):  
Megan H. Orzalli ◽  
Nicole M. Broekema ◽  
Benjamin A. Diner ◽  
Dustin C. Hancks ◽  
Nels C. Elde ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Human Fibroblasts ◽  
Interferon Γ ◽  
Viral Dna ◽  
Human Foreskin Fibroblasts ◽  
Infected Cells ◽  
Inducible Protein ◽  
The Stability ◽  
Simplex Virus

Interferon γ-inducible protein 16 (IFI16) and cGMP-AMP synthase (cGAS) have both been proposed to detect herpesviral DNA directly in herpes simplex virus (HSV)-infected cells and initiate interferon regulatory factor-3 signaling, but it has been unclear how two DNA sensors could both be required for this response. We therefore investigated their relative roles in human foreskin fibroblasts (HFFs) infected with HSV or transfected with plasmid DNA. siRNA depletion studies showed that both are required for the production of IFN in infected HFFs. We found that cGAS shows low production of cGMP-AMP in infected cells, but instead cGAS is partially nuclear in normal human fibroblasts and keratinocytes, interacts with IFI16 in fibroblasts, and promotes the stability of IFI16. IFI16 is associated with viral DNA and targets to viral genome complexes, consistent with it interacting directly with viral DNA. Our results demonstrate that IFI16 and cGAS cooperate in a novel way to sense nuclear herpesviral DNA and initiate innate signaling.

scholarly journals Inflammatory cytokines in major depressive disorder: A case–control study

2016 ◽  
Vol 51 (1) ◽  
pp. 23-31 ◽  
Author(s):  
Paolo Cassano ◽  
Eric Bui ◽  
Andrew H Rogers ◽  
Zandra E Walton ◽  
Rachel Ross ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Sampling Bias ◽  
Interferon Γ ◽  
Small Sample ◽  
Major Depressive ◽  
Course Of Illness ◽  
Luminex Technology ◽  
Cytokine Levels ◽  
Inducible Protein

Introduction: There is mixed evidence in the literature on the role of inflammation in major depressive disorder. Contradictory findings are attributed to lack of rigorous characterization of study subjects, to the presence of concomitant medical illnesses, to the small sample sizes, and to the limited number of cytokines tested. Methods: Subjects aged 18–70 years, diagnosed with major depressive disorder and presenting with chronic course of illness, as well as matched controls ( n = 236), were evaluated by trained raters and provided blood for cytokine measurements. Cytokine levels in EDTA plasma were measured with the MILLIPLEX Multi-Analyte Profiling Human Cytokine/Chemokine Assay employing Luminex technology. The Wilcoxon rank-sum test was used to compare cytokine levels between major depressive disorder subjects and healthy volunteers, before (interleukin [IL]-1β, IL-6, and tumor necrosis factor-α) and after Bonferroni correction for multiple comparisons (IL-1α, IL-2, IL-3, IL-4, IL-5, IL-7, IL-8, IL-10, IL-12(p40), IL-12(p70), IL-13, IL-15, IFN-γ-inducible protein 10, Eotaxin, interferon-γ, monotype chemoattractant protein-1, macrophage inflammatory protein-1α, granulocyte-macrophage colony-stimulating factor and vascular endothelial growth factor). Results: There were no significant differences in cytokine levels between major depressive disorder subjects and controls, both prior to and after correction for multiple analyses (significance set at p ⩽ 0.05 and p ⩽ 0.002, respectively). Conclusion: Our well-characterized examination of cytokine plasma levels did not support the association of major depressive disorder with systemic inflammation. The heterogeneity of major depressive disorder, as well as a potential sampling bias selecting for non-inflammatory depression, might have determined our findings discordant with the literature.

Interferon γ–Inducible Protein 10 Selectively Inhibits Proliferation and Induces Apoptosis in Endothelial Cells

2006 ◽  
Vol 13 (1) ◽  
pp. 125-133 ◽  
Author(s):  
Elizabeth D. Feldman ◽  
David M. Weinreich ◽  
Nancy M. Carroll ◽  
Monika L. Burness ◽  
Andrew L. Feldman ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Interferon Γ ◽  
Inducible Protein

scholarly journals Sustained expansion of NKT cells and antigen-specific T cells after injection of α-galactosyl-ceramide loaded mature dendritic cells in cancer patients

2005 ◽  
Vol 201 (9) ◽  
pp. 1503-1517 ◽  
Author(s):  
David H. Chang ◽  
Keren Osman ◽  
John Connolly ◽  
Anjli Kukreja ◽  
Joseph Krasovsky ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Advanced Cancer ◽  
Serum Levels ◽  
Nkt Cells ◽  
Interleukin 12 ◽  
Cell Immunity ◽  
Galactosyl Ceramide ◽  
Inducible Protein

Natural killer T (NKT) cells are distinct glycolipid reactive innate lymphocytes that are implicated in the resistance to pathogens and tumors. Earlier attempts to mobilize NKT cells, specifically, in vivo in humans met with limited success. Here, we evaluated intravenous injection of monocyte-derived mature DCs that were loaded with a synthetic NKT cell ligand, α-galactosyl-ceramide (α-GalCer; KRN-7000) in five patients who had advanced cancer. Injection of α-GalCer–pulsed, but not unpulsed, dendritic cells (DCs) led to >100-fold expansion of several subsets of NKT cells in all patients; these could be detected for up to 6 mo after vaccination. NKT activation was associated with an increase in serum levels of interleukin-12 p40 and IFN-γ inducible protein-10. In addition, there was an increase in memory CD8+ T cells specific for cytomegalovirus in vivo in response to α-GalCer–loaded DCs, but not unpulsed DCs. These data demonstrate the feasibility of sustained expansion of NKT cells in vivo in humans, including patients who have advanced cancer, and suggest that NKT activation might help to boost adaptive T cell immunity in vivo.

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