Role of purinergic receptors in hepatobiliary carcinoma in Pakistani population: an approach towards proinflammatory role of P2X4 and P2X7 receptors

Hematopoietic stem cells (HSCs) regularly produce various blood cells throughout life via their self-renewal, proliferation, and differentiation abilities. Most HSCs remain quiescent in the bone marrow (BM) and respond in a timely manner to either physiological or pathological cues, but the underlying mechanisms remain to be further elucidated. In the past few years, accumulating evidence has highlighted an intermediate role of inflammasome activation in hematopoietic maintenance, post-hematopoietic transplantation complications, and senescence. As a cytosolic protein complex, the inflammasome participates in immune responses by generating a caspase cascade and inducing cytokine secretion. This process is generally triggered by signals from purinergic receptors that integrate extracellular stimuli such as the metabolic factor ATP via P2 receptors. Furthermore, targeted modulation/inhibition of specific inflammasomes may help to maintain/restore adequate hematopoietic homeostasis. In this review, we will first summarize the possible relationships between inflammasome activation and homeostasis based on certain interesting phenomena. The cellular and molecular mechanism by which purinergic receptors integrate extracellular cues to activate inflammasomes inside HSCs will then be described. We will also discuss the therapeutic potential of targeting inflammasomes and their components in some diseases through pharmacological or genetic strategies.

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Expression and proinflammatory role of proteinase-activated receptor 2 in rheumatoid synovium: Ex vivo studies using a novel proteinase-activated receptor 2 antagonist

Arthritis & Rheumatism ◽

10.1002/art.22423 ◽

2007 ◽

Vol 56 (3) ◽

pp. 765-771 ◽

Cited By ~ 50

Author(s):

Elizabeth B. Kelso ◽

William R. Ferrell ◽

John C. Lockhart ◽

Iona Elias-Jones ◽

Todd Hembrough ◽

...

Keyword(s):

Ex Vivo ◽

Rheumatoid Synovium ◽

Proinflammatory Role

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ROLE OF PURINERGIC RECEPTORS IN CELL DEATH AND CYTOKINE RELEASE IN THE IMMUNE SYSTEM

Biochemical Society Transactions ◽

10.1042/bst024560sc ◽

1996 ◽

Vol 24 (4) ◽

pp. 560S-560S

Author(s):

Davide Ferrari ◽

Martin Villalba ◽

Paola Chiozzi ◽

Monica Dal Susino ◽

Simonetta Falzoni ◽

...

Keyword(s):

Cell Death ◽

Immune System ◽

Purinergic Receptors ◽

Cytokine Release

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The Role of Purinergic Receptors in Cancer-Induced Bone Pain

Journal of Osteoporosis ◽

10.1155/2012/758181 ◽

2012 ◽

Vol 2012 ◽

pp. 1-12 ◽

Cited By ~ 14

Author(s):

Sarah Falk ◽

Maria Uldall ◽

Anne-Marie Heegaard

Keyword(s):

Inflammatory Pain ◽

Bone Pain ◽

Purinergic Receptors ◽

Sensory Information ◽

Cellular Mechanisms ◽

Pain State ◽

Current Therapies ◽

Peripheral Site

Cancer-induced bone pain severely compromises the quality of life of many patients suffering from bone metastasis, as current therapies leave some patients with inadequate pain relief. The recent development of specific animal models has increased the understanding of the molecular and cellular mechanisms underlying cancer-induced bone pain including the involvement of ATP and the purinergic receptors in the progression of the pain state. In nociception, ATP acts as an extracellular messenger to transmit sensory information both at the peripheral site of tissue damage and in the spinal cord. Several of the purinergic receptors have been shown to be important for the development and maintenance of neuropathic and inflammatory pain, and studies have demonstrated the importance of both peripheral and central mechanisms. We here provide an overview of the current literature on the role of purinergic receptors in cancer-induced bone pain with emphasis on some of the difficulties related to studying this complex pain state.

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Characteristics and the role of purinergic receptors in pathophysiology with focus on immune response

International Reviews of Immunology ◽

10.1080/08830185.2020.1723582 ◽

2020 ◽

Vol 39 (3) ◽

pp. 97-117

Author(s):

Marharyta Zyma ◽

Rafał Pawliczak

Keyword(s):

Immune Response ◽

Purinergic Receptors

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EnteroaggregativeEscherichia coliAdherence Fimbriae Drive Inflammatory Cell Recruitment via Interactions with Epithelial MUC1

mBio ◽

10.1128/mbio.00717-17 ◽

2017 ◽

Vol 8 (3) ◽

Cited By ~ 13

Author(s):

Erik J. Boll ◽

Jorge Ayala-Lujan ◽

Rose L. Szabady ◽

Christopher Louissaint ◽

Rachel Z. Smith ◽

...

Keyword(s):

Intestinal Inflammation ◽

Inflammatory Responses ◽

Cell Receptor ◽

Host Cell Receptor ◽

Intestinal Infections ◽

Elevated Expression ◽

Intestinal Pathogen ◽

Proinflammatory Role ◽

First Time

ABSTRACTEnteroaggregativeEscherichia coli(EAEC) causes diarrhea and intestinal inflammation worldwide. EAEC strains are characterized by the presence of aggregative adherence fimbriae (AAF), which play a key role in pathogenesis by mediating attachment to the intestinal mucosa and by triggering host inflammatory responses. Here, we identify the epithelial transmembrane mucin MUC1 as an intestinal host cell receptor for EAEC, demonstrating that AAF-mediated interactions between EAEC and MUC1 facilitate enhanced bacterial adhesion. We further demonstrate that EAEC infection also causes elevated expression of MUC1 in inflamed human intestinal tissues. Moreover, we find that MUC1 facilitates AAF-dependent migration of neutrophils across the epithelium in response to EAEC infection. Thus, we show for the first time a proinflammatory role for MUC1 in the host response to an intestinal pathogen.IMPORTANCEEAEC is a clinically important intestinal pathogen that triggers intestinal inflammation and diarrheal illness via mechanisms that are not yet fully understood. Our findings provide new insight into how EAEC triggers host inflammation and underscores the pivotal role of AAFs—the principal adhesins of EAEC—in driving EAEC-associated disease. Most importantly, our findings add a new dimension to the signaling properties of the transmembrane mucin MUC1. Mostly studied for its role in various forms of cancer, MUC1 is widely regarded as playing an anti-inflammatory role in response to infection with bacterial pathogens in various tissues. However, the role of MUC1 during intestinal infections has not been previously explored, and our results describe the first report of MUC1 as a proinflammatory factor following intestinal infection.

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The Role of Uridine Adenosine Tetraphosphate in the Vascular System

Advances in Pharmacological Sciences ◽

10.1155/2011/435132 ◽

2011 ◽

Vol 2011 ◽

pp. 1-7 ◽

Cited By ~ 9

Author(s):

Takayuki Matsumoto ◽

Rita C. Tostes ◽

R. Clinton Webb

Keyword(s):

Smooth Muscle ◽

Cardiovascular Diseases ◽

Endothelial Dysfunction ◽

Arterial Hypertension ◽

Smooth Muscle Cells ◽

Vascular Function ◽

Purinergic Receptors ◽

Potential Role ◽

Vascular System

The endothelium plays a pivotal role in vascular homeostasis, and endothelial dysfunction is a major feature of cardiovascular diseases, such as arterial hypertension, atherosclerosis, and diabetes. Recently, uridine adenosine tetraphosphate (Up4A) has been identified as a novel and potent endothelium-derived contracting factor (EDCF). Up4A structurally contains both purine and pyrimidine moieties, which activate purinergic receptors. There is an accumulating body of evidence to show that Up4A modulates vascular function by actions on endothelial and smooth muscle cells. In this paper, we discuss the effects of Up4A on vascular function and a potential role for Up4A in cardiovascular diseases.

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B-Cell Activating Factor as a Cancer Biomarker and Its Implications in Cancer-Related Cachexia

BioMed Research International ◽

10.1155/2015/792187 ◽

2015 ◽

Vol 2015 ◽

pp. 1-9 ◽

Cited By ~ 7

Author(s):

Michal Rihacek ◽

Julie Bienertova-Vasku ◽

Dalibor Valik ◽

Jaroslav Sterba ◽

Katerina Pilatova ◽

...

Keyword(s):

B Cell ◽

Cancer Progression ◽

Lupus Erythematosus ◽

Cancer Cachexia ◽

Plasma Cells ◽

Ongoing Research ◽

B Cell Activating Factor ◽

Proinflammatory Role ◽

Cachexia Syndrome

B-cell activating factor (BAFF) is a cytokine and adipokine of the TNF ligand superfamily. The main biological function of BAFF in maintaining the maturation of B-cells to plasma cells has recently made it a target of the first FDA-approved selective BAFF antibody, belimumab, for the therapy of systemic lupus erythematosus. Concomitantly, the role of BAFF in cancer has been a subject of research since its discovery. Here we review BAFF as a biomarker of malignant disease activity and prognostic factor in B-cell derived malignancies such as multiple myeloma. Moreover, anti-BAFF therapy seems to be a promising approach in treatment of B-cell derived leukemias/lymphomas. In nonhematologic solid tumors, BAFF may contribute to cancer progression by mechanisms both dependent on and independent of BAFF’s proinflammatory role. We also describe ongoing research into the pathophysiological link between BAFF and cancer-related cachexia. BAFF has been shown to contribute to inflammation and insulin resistance which are known to worsen cancer cachexia syndrome. Taking all the above together, BAFF is emerging as a biomarker of several malignancies and a possible hallmark of cancer cachexia.

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