scholarly journals Pathophysiological Role of Extracellular Purinergic Mediators in the Control of Intestinal Inflammation

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Yosuke Kurashima ◽  
Hiroshi Kiyono ◽  
Jun Kunisawa
Keyword(s):  
Immune Cells ◽  
Purinergic Receptors ◽  
Intestinal Inflammation ◽  
P2y Receptors ◽  
P2x And P2y Receptors ◽  
Extracellular Compartment ◽  
Pathophysiological Role ◽  
Novel Targets ◽  
Irritable Bowel

Purinergic mediators such as adenosine 5′-triphosphate (ATP) are released into the extracellular compartment from damaged tissues and activated immune cells. They are then recognized by multiple purinergic P2X and P2Y receptors. Release and recognition of extracellular ATP are associated with both the development and the resolution of inflammation and infection. Accumulating evidence has recently suggested the potential of purinergic receptors as novel targets for drugs for treating intestinal disorders, including intestinal inflammation and irritable bowel syndrome. In this review, we highlight recent findings regarding the pathophysiological role of purinergic mediators in the development of intestinal inflammation.

scholarly journals Smad7 and Colorectal Carcinogenesis: A Double-Edged Sword

Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 612 ◽  
Author(s):  
Edoardo Troncone ◽  
Giovanni Monteleone
Keyword(s):  
Immune Cells ◽  
Transforming Growth Factor ◽  
Intestinal Inflammation ◽  
Association Studies ◽  
Cell Subset ◽  
Colorectal Carcinogenesis ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Chronic Intestinal Inflammation

Colorectal carcinogenesis is a complex process in which many immune and non-immune cells and a huge number of mediators are involved. Among these latter factors, Smad7, an inhibitor of the transforming growth factor (TGF)-β1 signaling that has been involved in the amplification of the inflammatory process sustaining chronic intestinal inflammation, is supposed to make a valid contribution to the growth and survival of colorectal cancer (CRC) cells. Smad7 is over-expressed by tumoral cells in both sporadic CRC and colitis-associated CRC, where it sustains neoplastic processes through activation of either TGFβ-dependent or non-dependent pathways. Consistently, genome-wide association studies have identified single nucleotide polymorphisms of the Smad7 gene associated with CRC and shown that either amplification or deletion of the Smad7 gene associates with a poor prognosis or better outcome, respectively. On the other hand, there is evidence that over-expression of Smad7 in immune cells infiltrating the inflamed gut of patients with inflammatory bowel disease can elicit anti-tumor responses, with the down-stream effect of attenuating CRC cell growth. Taken together, these observations suggest a double role of Smad7 in colorectal carcinogenesis, which probably depends on the cell subset and the biological context analyzed. In this review, we summarize the available evidences about the role of Smad7 in both sporadic and colitis-associated CRC.

Evidence on the pathogenic role of auto-antibodies in acute cardiovascular diseases

2013 ◽  
Vol 109 (05) ◽  
pp. 854-868 ◽  
Author(s):  
Federico Carbone ◽  
Alessio Nencioni ◽  
François Mach ◽  
Nicolas Vuilleumier ◽  
Fabrizio Montecucco
Keyword(s):  
Immune Cells ◽  
Atherosclerotic Plaques ◽  
Plaque Vulnerability ◽  
Pathogenic Role ◽  
Pathophysiological Role ◽  
Different Types ◽  
Inflammatory Processes ◽  
Oxidative Processes ◽  
Circulating Autoantibodies

SummaryAtherothrombosis is the major determinant of acute ischaemic cardiovascular events, such as myocardial infarction and stroke. Inflammatory processes have been linked to all phases of atherogenesis In particular, the identification of autoimmunity mediators in the complex microenvironment of chronic inflammation has become the focus of attention in both early and advanced atherogenic processes. Autoantibodies against self-molecules or new epitopes generated by oxidative processes infiltrate atherosclerotic plaques and were shown to modulate the activity of immune cells by binding various types of receptors. However, despite mounting evidence for a pathophysiological role of autoantibodies in atherothrombosis, the clinical relevance for circulating autoantibodies in cardiovascular outcomes is still debated. This review aims at illustrating the mechanisms by which different types of autoantibodies might either promote or repress atherothrombosis and to discuss the clinical studies assessing the role of auto-antibodies as prognostic biomarkers of plaque vulnerability.

scholarly journals Irritable bowel syndrome: pathophysiological role of intestinal dysbiosis and possibilities of its modulation

2018 ◽  
Vol 13 (1) ◽  
Author(s):  
Kubanich Aitbaev ◽  
Ilhom Murkamilov ◽  
Viktor Fomin ◽  
Furkat Yusupov ◽  
Nodira Redjapova ◽  
...  
Keyword(s):  
Irritable Bowel Syndrome ◽  
Intestinal Dysbiosis ◽  
Pathophysiological Role ◽  
Irritable Bowel

scholarly journals Role of HCA2 in Regulating Intestinal Homeostasis and Suppressing Colon Carcinogenesis

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhuoyue Li ◽  
Kayleen J. McCafferty ◽  
Robert L. Judd
Keyword(s):  
Immune Cells ◽  
Essential Role ◽  
Intestinal Inflammation ◽  
Intestinal Epithelial Cells ◽  
Physiological Role ◽  
Colon Carcinogenesis ◽  
Intestinal Epithelial ◽  
Intestinal Homeostasis ◽  
Exogenous Ligands

Hydroxycarboxylic acid receptor 2 (HCA2) is vital for sensing intermediates of metabolism, including β-hydroxybutyrate and butyrate. It also regulates profound anti-inflammatory effects in various tissues, indicating that HCA2 may serve as an essential therapeutic target for mediating inflammation-associated diseases. Butyrate and niacin, endogenous and exogenous ligands of HCA2, have been reported to play an essential role in maintaining intestinal homeostasis. HCA2, predominantly expressed in diverse immune cells, is also present in intestinal epithelial cells (IECs), where it regulates the intricate communication network between diet, microbiota, and immune cells. This review summarizes the physiological role of HCA2 in intestinal homeostasis and its pathological role in intestinal inflammation and cancer.

scholarly journals Inactive Rhomboid Protein 2 Mediates Intestinal Inflammation by Releasing Tumor Necrosis Factor–α

2019 ◽  
Vol 26 (2) ◽  
pp. 242-253
Author(s):  
Jee Hyun Kim ◽  
Sung Wook Hwang ◽  
Jaemoon Koh ◽  
Jaeyoung Chun ◽  
Changhyun Lee ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Immune Cells ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Intestinal Inflammation ◽  
Converting Enzyme ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Inactive rhomboid 2 (iRhom2) is an essential molecule required for the maturation of tumor necrosis factor–α–converting enzyme in immune cells, which regulates TNF-α release. The aim of this study was to investigate the role of iRhom2 in intestinal inflammation.

Learning the Roles of the Hepatic Adaptive Immune System in Hepatocellular Carcinoma—Nature's Guide for Successful Cancer Immunotherapy

2017 ◽  
Vol 37 (03) ◽  
pp. 210-218 ◽  
Author(s):  
Mathias Heikenwälder ◽  
Eli Pikarsky
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune System ◽  
Immune Cells ◽  
Protective Immunity ◽  
Adaptive Immune System ◽  
Hepatic Parenchyma ◽  
Adaptive Immune ◽  
Adaptive Immune Cells ◽  
Pathophysiological Role

AbstractThe different roles of the adaptive immune system in cancer are beginning to unfold. The dramatic responses to immune check point drugs in some tumors generated an accelerated need for understanding the complex set of interactions between tumor and immune cells. In view of the major pathophysiological role of immune cells in hepatocellular carcinoma, it is not surprising that malignant hepatocytes interact extensively with adaptive immune cells, resulting in both protumor immunopathology and antitumor protective immunity. Identifying potential responders to drugs that target the adaptive immune system, monitoring their immune response to the tumor, and devising the best treatment combinations depends on understanding the complex set of interactions taking place within the tumor and in the adjacent hepatic parenchyma.

Nucleotide-mediated calcium signaling in rat cortical astrocytes: Role of P2X and P2Y receptors

Glia ◽  
2003 ◽  
Vol 43 (3) ◽  
pp. 218-230 ◽  
Author(s):  
Marta Fumagalli ◽  
Roberta Brambilla ◽  
Nadia D'Ambrosi ◽  
Cinzia Volonté ◽  
Michela Matteoli ◽  
...  
Keyword(s):  
Calcium Signaling ◽  
P2y Receptors ◽  
P2x And P2y Receptors ◽  
Cortical Astrocytes

Role of P2X and P2Y receptors in rat myocardial contractility during ontogeny

2007 ◽  
Vol 143 (6) ◽  
pp. 695-698 ◽  
Author(s):  
T. A. Anikina ◽  
G. A. Bilalova ◽  
A. A. Zverev ◽  
F. G. Sitdikov
Keyword(s):  
Myocardial Contractility ◽  
P2y Receptors ◽  
P2x And P2y Receptors

Purinergic receptors in gastrointestinal inflammation

2008 ◽  
Vol 294 (2) ◽  
pp. G401-G410 ◽  
Author(s):  
Vasantha L. Kolachala ◽  
Rahul Bajaj ◽  
Meghana Chalasani ◽  
Shanthi V. Sitaraman
Keyword(s):  
Gastrointestinal Tract ◽  
Purinergic Receptors ◽  
Cell Activation ◽  
Intestinal Inflammation ◽  
Purinergic Receptor ◽  
Cell Types ◽  
Paracrine Signaling ◽  
Transmembrane Receptors ◽  
Therapeutic Modalities ◽  
Pathophysiological Role

Purinergic receptors comprise a family of transmembrane receptors that are activated by extracellular nucleosides and nucleotides. The two major classes of purinergic receptors, P1 and P2, are expressed widely in the gastrointestinal tract as well as immune cells. The purinergic receptors serve a variety of functions from acting as neurotransmitters, to autocoid and paracrine signaling, to cell activation and immune response. Nucleosides and nucleotide agonist of purinergic receptors are released by many cell types in response to specific physiological signals, and their levels are increased during inflammation. In the past decade, the advent of genetic knockout mice and the development of highly potent and selective agonists and antagonists for the purinergic receptors have significantly advanced the understanding of purinergic receptor signaling in health and inflammation. In fact, agonist/antagonists of purinergic receptors are emerging as therapeutic modalities to treat intestinal inflammation. In this article, the distribution of the purinergic receptors in the gastrointestinal tract and their physiological and pathophysiological role in intestinal inflammation will be reviewed.

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