scholarly journals The Multifaceted Functions of CXCL10 in Cardiovascular Disease

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Pleunie van den Borne ◽  
Paul H. A. Quax ◽  
Imo E. Hoefer ◽  
Gerard Pasterkamp
Keyword(s):  
Cardiovascular Disease ◽  
Inflammatory Responses ◽  
Clinical Settings ◽  
Key Features ◽  
Tissue Cells ◽  
Inducible Protein ◽  
Chemokine Family ◽  
Interferon Inducible Protein ◽  
Biological Actions

C-X-C motif ligand 10 (CXCL10), or interferon-inducible protein-10, is a small chemokine belonging to the CXC chemokine family. Its members are responsible for leukocyte trafficking and act on tissue cells, like endothelial and vascular smooth muscle cells. CXCL10 is secreted by leukocytes and tissue cells and functions as a chemoattractant, mainly for lymphocytes. After binding to its receptor CXCR3, CXCL10 evokes a range of inflammatory responses: key features in cardiovascular disease (CVD). The role of CXCL10 in CVD has been extensively described, for example for atherosclerosis, aneurysm formation, and myocardial infarction. However, there seems to be a discrepancy between experimental and clinical settings. This discrepancy occurs from differences in biological actions between species (e.g. mice and human), which is dependent on CXCL10 signaling via different CXCR3 isoforms or CXCR3-independent signaling. This makes translation from experimental to clinical settings challenging. Furthermore, the overall consensus on the actions of CXCL10 in specific CVD models is not yet reached. The purpose of this review is to describe the functions of CXCL10 in different CVDs in both experimental and clinical settings and to highlight and discuss the possible discrepancies and translational difficulties. Furthermore, CXCL10 as a possible biomarker in CVD will be discussed.

scholarly journals Human genetic deficiencies reveal the roles of complement in the inflammatory network: Lessons from nature

2009 ◽  
Vol 106 (37) ◽  
pp. 15861-15866 ◽  
Author(s):  
Knut Tore Lappegård ◽  
Dorte Christiansen ◽  
Anne Pharo ◽  
Ebbe Billmann Thorgersen ◽  
Bernt Christian Hellerud ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Gram Negative Bacteria ◽  
Enzyme Release ◽  
Experimental Conditions ◽  
Gram Negative ◽  
Cytokines And Chemokines ◽  
Ifn Γ ◽  
Inducible Protein ◽  
The Complement System

Complement component C5 is crucial for experimental animal inflammatory tissue damage; however, its involvement in human inflammation is incompletely understood. The responses to Gram-negative bacteria were here studied taking advantage of human genetic complement-deficiencies—nature's own knockouts—including a previously undescribed C5 defect. Such deficiencies provide a unique tool for investigating the biological role of proteins. The experimental conditions allowed cross-talk between the different inflammatory pathways using a whole blood model based on the anticoagulant lepirudin, which does not interfere with the complement system. Expression of tissue factor, cell adhesion molecules, and oxidative burst depended highly on C5, mediated through the activation product C5a, whereas granulocyte enzyme release relied mainly on C3 and was C5a-independent. Release of cytokines and chemokines was mediated to varying degrees by complement and CD14; for example, interleukin (IL)-1β and IL-8 were more dependent on complement than IFN-γ and IL-6, which were highly dependent on CD14. IL-1 receptor antagonist (IL-1ra) and IFN-γ inducible protein 10 (IP-10) were fully dependent on CD14 and inversely regulated by complement, that is, complement deficiency and complement inhibition enhanced their release. Granulocyte responses were mainly complement-dependent, whereas monocyte responses were more dependent on CD14. Notably, all responses were abolished by combined neutralization of complement and CD14. The present study provides important insight into the comprehensive role of complement in human inflammatory responses to Gram-negative bacteria.

scholarly journals Overexpression of Interferon-Inducible Protein 16 Promotes Progression of Human Pancreatic Adenocarcinoma Through Interleukin-1β-Induced Tumor-Associated Macrophage Infiltration in the Tumor Microenvironment

2021 ◽  
Vol 9 ◽  
Author(s):  
Jing-Xian Chen ◽  
Chien-Shan Cheng ◽  
Hong-Fang Gao ◽  
Zi-Jie Chen ◽  
Ling-Ling Lv ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Growth ◽  
Conditioned Medium ◽  
Pancreatic Adenocarcinoma ◽  
Human Pancreatic Adenocarcinoma ◽  
Inducible Protein ◽  
And Migration ◽  
Interferon Inducible Protein ◽  
Proliferation And Migration

Activation of inflammasomes has been reported in human pancreatic adenocarcinoma (PAAD); however, the expression pattern and functional role of inflammasome-related proteins in PAAD have yet to be identified. In this study, we systemically examined the expression and role of different inflammasome proteins by retrieving human expression data. Several genes were found to be differentially expressed; however, only interferon-inducible protein 16 (IFI16) expression was found to be adversely correlated with the overall survival of PAAD patients. Overexpression of IFI16 significantly promoted tumor growth, increased tumor size and weight in the experimental PAAD model of mice, and specifically increased the population of tumor-associated macrophages (TAMs) in the tumor microenvironment. Depletion of TAMs by injection of liposome clodronate attenuated the IFI16 overexpression-induced tumor growth in PAAD. In vitro treatment of conditioned medium from IFI16-overexpressing PAAD cells induced maturation, proliferation, and migration of bone marrow-derived monocytes, suggesting that IFI16 overexpression resulted in cytokine secretion that favored the TAM population. Further analysis suggested that IFI16 overexpression activated inflammasomes, thereby increasing the release of IL-1β. Neutralization of IL-1β attenuated TAM maturation, proliferation, and migration induced by the conditioned medium from IFI16-overexpressing PAAD cells. Additionally, knockdown of IFI16 could significantly potentiate gemcitabine treatment in PAAD, which may be associated with the reduced infiltration of TAMs in the tumor microenvironment. The findings of our study shed light on the role of IFI16 as a potential therapeutic target for PAAD.

scholarly journals Metabolic Syndrome: The Complex Relationship of Diet to Conditions of Disturbed Metabolism

2011 ◽  
Vol 1 (2) ◽  
pp. 1 ◽  
Author(s):  
Jeffrey S. Bland
Keyword(s):  
Cardiovascular Disease ◽  
Metabolic Syndrome ◽  
Clinical Studies ◽  
Inflammatory Responses ◽  
Lifestyle Modification ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Public Health Challenge ◽  
Relationship Of

The widespread prevalence and deleterious effects of metabolic syndrome have become a major public health challenge as it is associated with the development of type 2 diabetes and cardiovascular disease. Lifestyle modification focusing on diet has shown promise for managing cardiovascular disease risk, and clinical studies provide evidence that a Mediterranean diet supplemented with phytochemicals is a successful interventional approach. The role of phytochemicals in regulating gene expression and modulating intracellular kinase activity has only recently begun to be appreciated. Clinical studies investigating the effects of specific phytochemicals in metabolic syndrome patients have produced encouraging results, including normalization of metabolic function, reduction of cardiovascular risk, and resolution of metabolic syndrome. As research advances our understanding of the evolutionary relationships between plants and humans, details are emerging about the mechanisms by which phytochemicals regulate insulin signaling and inflammatory responses. This expanding field of research is likely to lead to novel, effective clinical approaches for combating chronic diseases such as metabolic syndrome.

scholarly journals Inhibition of angiogenesis by interleukin-12 is mediated by the interferon-inducible protein 10

Blood ◽  
1996 ◽  
Vol 87 (9) ◽  
pp. 3877-3882 ◽  
Author(s):  
C Sgadari ◽  
AL Angiolillo ◽  
G Tosato
Keyword(s):  
Interleukin 12 ◽  
Human Interferon ◽  
Ifn Gamma ◽  
Mouse Splenocytes ◽  
Angiogenesis Inhibition ◽  
Inhibition Of Angiogenesis ◽  
Inducible Protein ◽  
Interferon Inducible Protein

Interleukin 12 (IL-12), a multifunctional cytokine produced by macrophages and B-cell lines, induces interferon-gamma (IFN-gamma) production, stimulates growth of both T and natural killer cells, promotes Th1-type helper T-cell responses, and inhibits neovascularization. Because the human interferon-inducible protein 10 (IP-10) can also inhibit neovascularization, we tested whether IP-10, induced by IL-12 through the intermediate IFN-gamma, might be a mediator of IL-12 angiogenesis inhibition. We report here that murine IL-12 profoundly inhibited basic fibroblast growth factor (bFGF)- induced Matrigel neovascularization in vivo, and that this effect of IL- 12 was neutralized by systemic administration of antibodies to either murine IFN-gamma or IP-10. Murine IL-12 induced murine IP-10 expression in mouse splenocytes, and human IFN-gamma induced human IP-10 expression in purified human endothelial cells, suggesting that IL-12 can induce IP-10 expression in certain cells. These results document the important role of IP-10 as a mediator of angiogenesis inhibition by IL-12, and raise the possibility that IP-10 may also contribute to the antitumor effect of IL-12.

Estrogens and human cardiovascular physiology

2001 ◽  
Vol 13 (4) ◽  
pp. 261 ◽  
Author(s):  
Paul A. Komesaroff ◽  
Krishnankutty Sudhir
Keyword(s):  
Cardiovascular Disease ◽  
Cardiovascular System ◽  
Mechanisms Of Action ◽  
Normal Male ◽  
Cardiovascular Physiology ◽  
Men And Women ◽  
Chronic Effects ◽  
Acute And Chronic Effects ◽  
Biological Actions

The importance of estrogens for cardiovascular physiology in women is accepted, even if the clinical place for hormonal supplementation after menopause remains uncertain. However, although men produce significant quantities of estrogen, relatively little is known about the role of estrogens in the male cardiovascular system. Recent evidence about the epidemiology of cardiovascular disease, the mechanisms of action of estrogens, the biological actions of endogenously produced estrogens in men, and the acute and chronic effects of estrogens on the vasculature in both men and women, suggests that these hormones may well play an important role in normal male cardiovascular physiology. In addition, they may provide useful adjuncts to therapy in selected groups of men.

scholarly journals Practical guidance for echocardiography for cancer therapeutics-related cardiac dysfunction

2020 ◽  
Author(s):  
Tetsuari Onishi ◽  
◽  
Yuko Fukuda ◽  
Sakiko Miyazaki ◽  
Hirotsugu Yamada ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Cancer Treatment ◽  
Cancer Therapeutics ◽  
Medical System ◽  
Clinical Settings ◽  
Patients With Cancer ◽  
Early Diagnosis Of Cancer ◽  
Diagnosis Of Cancer ◽  
Practical Guidance

Abstract The prognosis of patients with cancer has improved due to an early diagnosis of cancer and advances in cancer treatment. There are emerging reports on cardiotoxicity in cancer treatment and on cardiovascular disease in cancer patients, from which cardiovascular disease has been recognized as a common cause of death among cancer survivors. This situation has led to the need for a medical system in which oncologists and cardiologists work together to treat patients. With the growing importance of onco-cardiology, the role of echocardiography in cancer care is rapidly expanding, but at present, the practice of echocardiography in clinical settings varies from institution to institution, and is empirical with no established systematic guidance. In view of these circumstances, we thought that brief guidance for clinical application was necessary and have therefore developed this guidance, although evidence in this field is still insufficient.

scholarly journals Structural analysis of the HIN1 domain of interferon-inducible protein 204

2019 ◽  
Vol 75 (6) ◽  
pp. 455-460 ◽  
Author(s):  
Yuan Tian ◽  
Qian Yin
Keyword(s):  
Dna Binding ◽  
Inflammatory Responses ◽  
Binding Mode ◽  
Cell Proliferation And Differentiation ◽  
Surface Charge Distribution ◽  
Proliferation And Differentiation ◽  
Dna Binding Affinity ◽  
Inducible Protein ◽  
Microbial Dna ◽  
Interferon Inducible Protein

Interferon-inducible protein 204 (p204) binds to microbial DNA to elicit inflammatory responses and induce interferon production. p204 also modulates cell proliferation and differentiation by regulating various transcription factors. The C-terminal HIN domains in p204 are believed to be responsible for DNA binding, but the binding mode is not fully understood. The DNA-binding affinity of the p204 HIN1 domain has been characterized and its crystal structure has been determined, providing insight into its interaction with DNA. Surface-charge distribution together with sequence alignment suggests that the p204 HIN domain uses its L12 and L45 loops for DNA binding.

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