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Old and New Players in Inflammatory Disorders—in Memory of Dr. Nadia Ferlazzo

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Immunology".

Deadline for manuscript submissions: closed (30 June 2022) | Viewed by 40573

Special Issue Editor

Dr. Monica Currò

E-Mail Website
Guest Editor
Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Messina, Italy
Interests: biomarkers; cancer biology; hyperhomocysteinemia; hypoxia; inflammation; neuroprotection; transglutaminase
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Inflammation participates in host defenses against infectious agents and injury, but it also contributes to the development of many diseases that collectively represent the leading causes of disability and mortality worldwide. In particular, multiple lines of evidence have suggested that chronic diseases such as obesity, cardiovascular disease, type 2 diabetes mellitus, nonalcoholic fatty liver disease, autoimmunity, cancer, and neurodegenerative disorders recognize inflammation as a common trigger for pathophysiological conditions. However, the mechanisms underlying the inflammatory regulation of these disorders are not fully understood. The interplay of cells involved in the immune system and inflammatory mediators orchestrates molecular pathways that contribute to tissue injury, oxidative stress, remodeling of the extracellular matrix, angiogenesis, and fibrosis in target tissues.

As the control of inflammation seems to be an attractive target for healthcare improvement, a thorough knowledge of molecular profiles and the detection of new biomarkers of inflammatory processes can support the development of new approaches to early diagnosis, treatment, and monitoring of inflammation-related disorders, and also provide tools to predict disease susceptibility.

This Special Issue “Old and New Players in Inflammatory Disorders as Powerful Tools for Prevention, Diagnosis, and Treatment” welcomes original research and review articles in the field, with a focus on but not limited to molecular players in inflammation that hold the potential for making advancements in the management of inflammatory diseases.

Dr. Monica Currò
Guest Editor

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • immunomodulatory effectors
  • peripheral inflammation molecular profiles
  • signal transduction
  • oxidative stress-related inflammation
  • chronic inflammation-associated oncogenic players
  • gut microbiota–immunity axis
  • anti-inflammatory agents
  • promising biomarkers in inflammation-related diseases

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Published Papers (12 papers)

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Research

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16 pages, 3965 KiB  
Article
Effect of Multiple Sclerosis Cerebrospinal Fluid and Oligodendroglia Cell Line Environment on Human Wharton’s Jelly Mesenchymal Stem Cells Secretome
by Karolina Salwierak-Głośna, Paweł Piątek, Małgorzata Domowicz and Mariola Świderek-Matysiak
Int. J. Mol. Sci. 2022, 23(4), 2177; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23042177 - 16 Feb 2022
Cited by 1 | Viewed by 1768
Abstract
Multiple sclerosis (MS) is a neurological disorder of autoimmune aetiology. Experimental therapies with the use of mesenchymal stem cells (MSCs) have emerged as a response to the unmet need for new treatment options. The unique immunomodulatory features of stem cells obtained from Wharton’s [...] Read more.
Multiple sclerosis (MS) is a neurological disorder of autoimmune aetiology. Experimental therapies with the use of mesenchymal stem cells (MSCs) have emerged as a response to the unmet need for new treatment options. The unique immunomodulatory features of stem cells obtained from Wharton’s jelly (WJ-MSCs) make them an interesting research and therapeutic model. Most WJ-MSCs transplants for multiple sclerosis use intrathecal administration. We studied the effect of cerebrospinal fluid (CSF) obtained from MS patients on the secretory activity of WJ-MSCs and broaden this observation with WJ-MSCs interactions with human oligodendroglia cell line (OLs). Analysis of the WJ-MSCs secretory activity with use of Bio-Plex Pro™ Human Cytokine confirmed significant and diverse immunomodulatory potential. Our data reveal rich WJ-MSCs secretome with markedly increased levels of IL-6, IL-8, IP-10 and MCP-1 synthesis and a favourable profile of growth factors. The addition of MS CSF to the WJ-MSCs culture caused depletion of most proteins measured, only IL-12, RANTES and GM-CSF levels were increased. Most cytokines and chemokines decreased their concentrations in WJ-MSCs co-cultured with OLs, only eotaxin and RANTES levels were slightly increased. These results emphasize the spectrum of the immunomodulatory properties of WJ-MSCs and show how those effects can be modulated depending on the transplantation milieu. Full article
(This article belongs to the Special Issue Old and New Players in Inflammatory Disorders—in Memory of Dr. Nadia Ferlazzo)
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17 pages, 3745 KiB  
Article
Oleacein Attenuates Lipopolysaccharide-Induced Inflammation in THP-1-Derived Macrophages by the Inhibition of TLR4/MyD88/NF-κB Pathway
by Santa Cirmi, Alessandro Maugeri, Caterina Russo, Laura Musumeci, Michele Navarra and Giovanni Enrico Lombardo
Int. J. Mol. Sci. 2022, 23(3), 1206; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23031206 - 21 Jan 2022
Cited by 19 | Viewed by 2321
Abstract
It is known that plant phenolic compounds exert anti-inflammatory activity through both anti-oxidant effects and modulation of pivotal pro-inflammatory factors. Recently, Olea europaea has been studied as a natural source of bioactive molecules; however, few studies have focused on the biological effect of [...] Read more.
It is known that plant phenolic compounds exert anti-inflammatory activity through both anti-oxidant effects and modulation of pivotal pro-inflammatory factors. Recently, Olea europaea has been studied as a natural source of bioactive molecules; however, few studies have focused on the biological effect of oleacein (OLC), the most abundant secoiridoid. Therefore, the aim of this study was to investigate the potential anti-oxidant activity of OLC, as well as to study its anti-inflammatory effect in lipopolysaccharide (LPS)-stimulated THP-1-derived macrophages. LPS brought a dramatic increase of both release and gene expression of pro-inflammatory cytokines (IL-6, IL-1β and TNF-α), as well as a decrease of anti-inflammatory ones (IL-10), the effects of which are reverted by OLC. Moreover, it reduced the levels of COX-2, NO and PGE2 elicited by LPS exposure in THP-1 macrophages. Interestingly, OLC modulated inflammatory signaling pathways through the inhibition of CD14/TLR4/CD14/MyD88 axis and the activation of NF-κB. Finally, OLC showed relevant anti-oxidant capability, assessed by abiotic assays, and reduced the intracellular amount of ROS generated by LPS exposure in THP-1 macrophages. Overall, these results suggest that the anti-oxidant activity and anti-inflammatory effect of OLC may cooperate in its protective effect against inflammatory stressors, thus being a possible alternative pharmacological strategy aimed at reducing the inflammatory process. Full article
(This article belongs to the Special Issue Old and New Players in Inflammatory Disorders—in Memory of Dr. Nadia Ferlazzo)
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21 pages, 3367 KiB  
Article
Caulerpin Mitigates Helicobacter pylori-Induced Inflammation via Formyl Peptide Receptors
by Paola Cuomo, Chiara Medaglia, Ivana Allocca, Angela Michela Immacolata Montone, Fabrizia Guerra, Serena Cabaro, Ernesto Mollo, Daniela Eletto, Marina Papaianni and Rosanna Capparelli
Int. J. Mol. Sci. 2021, 22(23), 13154; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222313154 - 05 Dec 2021
Cited by 3 | Viewed by 2589
Abstract
The identification of novel strategies to control Helicobacter pylori (Hp)-associated chronic inflammation is, at present, a considerable challenge. Here, we attempt to combat this issue by modulating the innate immune response, targeting formyl peptide receptors (FPRs), G-protein coupled receptors that play [...] Read more.
The identification of novel strategies to control Helicobacter pylori (Hp)-associated chronic inflammation is, at present, a considerable challenge. Here, we attempt to combat this issue by modulating the innate immune response, targeting formyl peptide receptors (FPRs), G-protein coupled receptors that play key roles in both the regulation and the resolution of the innate inflammatory response. Specifically, we investigated, in vitro, whether Caulerpin—a bis-indole alkaloid isolated from algae of the genus Caulerpa—could act as a molecular antagonist scaffold of FPRs. We showed that Caulerpin significantly reduces the immune response against Hp culture filtrate, by reverting the FPR2-related signaling cascade and thus counteracting the inflammatory reaction triggered by Hp peptide Hp(2–20). Our study suggests Caulerpin to be a promising therapeutic or adjuvant agent for the attenuation of inflammation triggered by Hp infection, as well as its related adverse clinical outcomes. Full article
(This article belongs to the Special Issue Old and New Players in Inflammatory Disorders—in Memory of Dr. Nadia Ferlazzo)
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14 pages, 2348 KiB  
Article
Homocysteine Solution-Induced Response in Aerosol Jet Printed OECTs by Means of Gold and Platinum Gate Electrodes
by Pasquale D’Angelo, Mario Barra, Patrizia Lombari, Annapaola Coppola, Davide Vurro, Giuseppe Tarabella, Simone Luigi Marasso, Margherita Borriello, Federico Chianese, Alessandra F. Perna, Antonio Cassinese and Diego Ingrosso
Int. J. Mol. Sci. 2021, 22(21), 11507; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222111507 - 25 Oct 2021
Cited by 2 | Viewed by 1908
Abstract
Homocysteine (Hcy) is a non-protein, sulfur-containing amino acid, which is recognized as a possible risk factor for coronary artery and other pathologies when its levels in the blood exceed the normal range of between 5 and 12 μmol/L (hyperhomocysteinemia). At present, standard procedures [...] Read more.
Homocysteine (Hcy) is a non-protein, sulfur-containing amino acid, which is recognized as a possible risk factor for coronary artery and other pathologies when its levels in the blood exceed the normal range of between 5 and 12 μmol/L (hyperhomocysteinemia). At present, standard procedures in laboratory medicine, such as high-performance liquid chromatography (HPLC), are commonly employed for the quantitation of total Hcy (tHcy), i.e., the sum of the protein-bound (oxidized) and free (homocystine plus reduced Hcy) forms, in biological fluids (particularly, serum or plasma). Here, the response of Aerosol Jet-printed organic electrochemical transistors (OECTs), in the presence of either reduced (free) and oxidized Hcy-based solutions, was analyzed. Two different experimental protocols were followed to this end: the former consisting of gold (Au) electrodes’ biothiol-induced thiolation, while the latter simply used bare platinum (Pt) electrodes. Electrochemical impedance spectroscopy (EIS) analysis was performed both to validate the gold thiolation protocol and to gain insights into the reduced Hcy sensing mechanism by the Au-gated OECTs, which provided a final limit of detection (LoD) of 80 nM. For the OECT response based on Platinum gate electrodes, on the other hand, a LoD of 180 nM was found in the presence of albumin-bound Hcy, with this being the most abundant oxidized Hcy-form (i.e., the protein-bound form) in physiological fluids. Despite the lack of any biochemical functionalization supporting the response selectivity, the findings discussed in this work highlight the potential role of OECT in the development of low-cost point-of-care (POC) electronic platforms that are suitable for the evaluation, in humans, of Hcy levels within the physiological range and in cases of hyperhomocysteinemia. Full article
(This article belongs to the Special Issue Old and New Players in Inflammatory Disorders—in Memory of Dr. Nadia Ferlazzo)
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19 pages, 3282 KiB  
Article
Novel Insights into Epigenetic Regulation of IL6 Pathway: In Silico Perspective on Inflammation and Cancer Relationship
by Saverio Candido, Barbara Maria Rita Tomasello, Alessandro Lavoro, Luca Falzone, Giuseppe Gattuso and Massimo Libra
Int. J. Mol. Sci. 2021, 22(18), 10172; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms221810172 - 21 Sep 2021
Cited by 29 | Viewed by 2600
Abstract
IL-6 pathway is abnormally hyperactivated in several cancers triggering tumor cell growth and immune system inhibition. Along with genomic mutation, the IL6 pathway gene expression can be affected by DNA methylation, microRNAs, and post-translational modifications. Computational analysis was performed on the Cancer Genome [...] Read more.
IL-6 pathway is abnormally hyperactivated in several cancers triggering tumor cell growth and immune system inhibition. Along with genomic mutation, the IL6 pathway gene expression can be affected by DNA methylation, microRNAs, and post-translational modifications. Computational analysis was performed on the Cancer Genome Atlas (TCGA) datasets to explore the role of IL6, IL6R, IL6ST, and IL6R transmembrane isoform expression and their epigenetic regulation in different cancer types. IL6 was significantly modulated in 70% of tumor types, revealing either up- or down-regulation in an approximately equal number of tumors. Furthermore, IL6R and IL6ST were downregulated in more than 10 tumors. Interestingly, the correlation analysis demonstrated that only the IL6R expression was negatively affected by the DNA methylation within the promoter region in most tumors. Meanwhile, only the IL6ST expression was extensively modulated by miRNAs including miR-182-5p, which also directly targeted all three genes. In addition, IL6 upregulated miR-181a-3p, mirR-214-3p, miR-18a-5p, and miR-938, which in turn inhibited the expression of IL6 receptors. Finally, the patients’ survival rate was significantly affected by analyzed targets in some tumors. Our results suggest the relevance of epigenetic regulation of IL6 signaling and pave the way for further studies to validate these findings and to assess the prognostic and therapeutic predictive value of these epigenetic markers on the clinical outcome and survival of cancer patients. Full article
(This article belongs to the Special Issue Old and New Players in Inflammatory Disorders—in Memory of Dr. Nadia Ferlazzo)
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Review

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15 pages, 1248 KiB  
Review
Potential Inflammatory Biomarker in Patients with Attention Deficit Hyperactivity Disorder
by Ji Hyun Park
Int. J. Mol. Sci. 2022, 23(21), 13054; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms232113054 - 27 Oct 2022
Cited by 4 | Viewed by 3038
Abstract
Attention deficit hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder that can diminish the quality of life of both children and adults in academic, occupational, and social contexts. The kynurenine pathway (KP) contains a set of enzymatic reactions involved in tryptophan (TRP) degradation. [...] Read more.
Attention deficit hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder that can diminish the quality of life of both children and adults in academic, occupational, and social contexts. The kynurenine pathway (KP) contains a set of enzymatic reactions involved in tryptophan (TRP) degradation. It is known to be associated with the risk of developing ADHD. This review will address the KP and underlying mechanism of inflammation in ADHD. Potential inflammatory biomarkers reported in the most recent studies are summarized. Although a strong neuroimmunological basis has been established due to the advances of recent neurobiological research, the pathophysiology of ADHD remains unclear. Full article
(This article belongs to the Special Issue Old and New Players in Inflammatory Disorders—in Memory of Dr. Nadia Ferlazzo)
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18 pages, 1452 KiB  
Review
The Role of Macrophages in Liver Fibrosis: New Therapeutic Opportunities
by Eleonora Binatti, Alessio Gerussi, Donatella Barisani and Pietro Invernizzi
Int. J. Mol. Sci. 2022, 23(12), 6649; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23126649 - 14 Jun 2022
Cited by 20 | Viewed by 4944
Abstract
Chronic inflammation is the hallmark of fibrotic disorders and is characterized by the activation of immune cells in the damaged tissues. Macrophages have emerged as central players in the fibrotic process since they initiate, sustain and amplify the inflammatory reaction. As regards the [...] Read more.
Chronic inflammation is the hallmark of fibrotic disorders and is characterized by the activation of immune cells in the damaged tissues. Macrophages have emerged as central players in the fibrotic process since they initiate, sustain and amplify the inflammatory reaction. As regards the liver, distinct populations of phagocytic cells, like Kupffer cells and monocyte-derived macrophages, are indisputably key cells implicated in the pathogenesis of several chronic liver diseases. In this review, we summarize the current knowledge on the origin, role and functions of macrophages in fibrotic conditions, with a specific focus on liver fibrosis; then, we discuss some innovative therapeutic strategies targeting macrophages in fibrotic liver diseases. Full article
(This article belongs to the Special Issue Old and New Players in Inflammatory Disorders—in Memory of Dr. Nadia Ferlazzo)
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19 pages, 1180 KiB  
Review
TRPA1 Role in Inflammatory Disorders: What Is Known So Far?
by Lorenzo Landini, Daniel Souza Monteiro de Araujo, Mustafa Titiz, Pierangelo Geppetti, Romina Nassini and Francesco De Logu
Int. J. Mol. Sci. 2022, 23(9), 4529; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23094529 - 20 Apr 2022
Cited by 14 | Viewed by 5749
Abstract
The transient receptor potential ankyrin 1 (TRPA1), a member of the TRP superfamily of channels, is primarily localized in a subpopulation of primary sensory neurons of the trigeminal, vagal, and dorsal root ganglia, where its activation mediates neurogenic inflammatory responses. TRPA1 expression in [...] Read more.
The transient receptor potential ankyrin 1 (TRPA1), a member of the TRP superfamily of channels, is primarily localized in a subpopulation of primary sensory neurons of the trigeminal, vagal, and dorsal root ganglia, where its activation mediates neurogenic inflammatory responses. TRPA1 expression in resident tissue cells, inflammatory, and immune cells, through the indirect modulation of a large series of intracellular pathways, orchestrates a range of cellular processes, such as cytokine production, cell differentiation, and cytotoxicity. Therefore, the TRPA1 pathway has been proposed as a protective mechanism to detect and respond to harmful agents in various pathological conditions, including several inflammatory diseases. Specific attention has been paid to TRPA1 contribution to the transition of inflammation and immune responses from an early defensive response to a chronic pathological condition. In this view, TRPA1 antagonists may be regarded as beneficial tools for the treatment of inflammatory conditions. Full article
(This article belongs to the Special Issue Old and New Players in Inflammatory Disorders—in Memory of Dr. Nadia Ferlazzo)
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18 pages, 649 KiB  
Review
The Role of Inflammasomes in Glomerulonephritis
by Paula Anton-Pampols, Clara Diaz-Requena, Laura Martinez-Valenzuela, Francisco Gomez-Preciado, Xavier Fulladosa, Anna Vidal-Alabro, Joan Torras, Núria Lloberas and Juliana Draibe
Int. J. Mol. Sci. 2022, 23(8), 4208; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23084208 - 11 Apr 2022
Cited by 16 | Viewed by 3520
Abstract
The inflammasome is an immune multiprotein complex that activates pro-caspase 1 in response to inflammation-inducing stimuli and it leads to IL-1β and IL-18 proinflammatory cytokine production. NLRP1 and NLRP3 inflammasomes are the best characterized and they have been related to several autoimmune diseases. [...] Read more.
The inflammasome is an immune multiprotein complex that activates pro-caspase 1 in response to inflammation-inducing stimuli and it leads to IL-1β and IL-18 proinflammatory cytokine production. NLRP1 and NLRP3 inflammasomes are the best characterized and they have been related to several autoimmune diseases. It is well known that the kidney expresses inflammasome genes, which can influence the development of some glomerulonephritis, such as lupus nephritis, ANCA glomerulonephritis, IgA nephropathy and anti-GBM nephropathy. Polymorphisms of these genes have also been described to play a role in autoimmune and kidney diseases. In this review, we describe the main characteristics, activation mechanisms, regulation and functions of the different inflammasomes. Moreover, we discuss the latest findings about the role of the inflammasome in several glomerulonephritis from three different points of view: in vitro, animal and human studies. Full article
(This article belongs to the Special Issue Old and New Players in Inflammatory Disorders—in Memory of Dr. Nadia Ferlazzo)
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14 pages, 590 KiB  
Review
CD8+ T Cell Senescence: Lights and Shadows in Viral Infections, Autoimmune Disorders and Cancer
by Valentina Tedeschi, Giorgia Paldino, Martina Kunkl, Marino Paroli, Rosa Sorrentino, Loretta Tuosto and Maria Teresa Fiorillo
Int. J. Mol. Sci. 2022, 23(6), 3374; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23063374 - 21 Mar 2022
Cited by 25 | Viewed by 4784
Abstract
CD8+ T lymphocytes are a heterogeneous class of cells that play a crucial role in the adaptive immune response against pathogens and cancer. During their lifetime, they acquire cytotoxic functions to ensure the clearance of infected or transformed cells and, in addition, [...] Read more.
CD8+ T lymphocytes are a heterogeneous class of cells that play a crucial role in the adaptive immune response against pathogens and cancer. During their lifetime, they acquire cytotoxic functions to ensure the clearance of infected or transformed cells and, in addition, they turn into memory lymphocytes, thus providing a long-term protection. During ageing, the thymic involution causes a reduction of circulating T cells and an enrichment of memory cells, partially explaining the lowering of the response towards novel antigens with implications in vaccine efficacy. Moreover, the persistent stimulation by several antigens throughout life favors the switching of CD8+ T cells towards a senescent phenotype contributing to a low-grade inflammation that is a major component of several ageing-related diseases. In genetically predisposed young people, an immunological stress caused by viral infections (e.g., HIV, CMV, SARS-CoV-2), autoimmune disorders or tumor microenvironment (TME) could mimic the ageing status with the consequent acceleration of T cell senescence. This, in turn, exacerbates the inflamed conditions with dramatic effects on the clinical progression of the disease. A better characterization of the phenotype as well as the functions of senescent CD8+ T cells can be pivotal to prevent age-related diseases, to improve vaccine strategies and, possibly, immunotherapies in autoimmune diseases and cancer. Full article
(This article belongs to the Special Issue Old and New Players in Inflammatory Disorders—in Memory of Dr. Nadia Ferlazzo)
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14 pages, 490 KiB  
Review
Atherosclerosis in HIV Patients: What Do We Know so Far?
by Anastasia V. Poznyak, Evgeny E. Bezsonov, Evgeny E. Borisov, Andrey V. Grechko, Andrey G. Kartuesov and Alexander N. Orekhov
Int. J. Mol. Sci. 2022, 23(5), 2504; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23052504 - 24 Feb 2022
Cited by 13 | Viewed by 2137
Abstract
For the past several decades, humanity has been dealing with HIV. This disease is one of the biggest global health problems. Fortunately, modern antiretroviral therapy allows patients to manage the disease, improving their quality of life and their life expectancy. In addition, the [...] Read more.
For the past several decades, humanity has been dealing with HIV. This disease is one of the biggest global health problems. Fortunately, modern antiretroviral therapy allows patients to manage the disease, improving their quality of life and their life expectancy. In addition, the use of these drugs makes it possible to reduce the risk of transmission of the virus to almost zero. Atherosclerosis is another serious pathology that leads to severe health problems, including disability and, often, the death of the patient. An effective treatment for atherosclerosis has not yet been developed. Both types of immune response, innate and adaptive, are important components of the pathogenesis of this disease. In this regard, the peculiarities of the development of atherosclerosis in HIV carriers are of particular scientific interest. In this review, we have tried to summarize the data on atherosclerosis and its development in HIV carriers. We also looked at the classic therapeutic methods and their features concerning the concomitant diagnosis. Full article
(This article belongs to the Special Issue Old and New Players in Inflammatory Disorders—in Memory of Dr. Nadia Ferlazzo)
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10 pages, 987 KiB  
Review
Antibodies against Angiotensin II Type 1 and Endothelin 1 Type A Receptors in Cardiovascular Pathologies
by Giovanni Civieri, Laura Iop and Francesco Tona
Int. J. Mol. Sci. 2022, 23(2), 927; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23020927 - 15 Jan 2022
Cited by 17 | Viewed by 3464
Abstract
Angiotensin II receptor type 1 (AT1R) and endothelin-1 receptor type A (ETAR) are G-protein-coupled receptors (GPCRs) expressed on the surface of a great variety of cells: immune cells, vascular smooth cells, endothelial cells, and fibroblasts express ETAR and AT1R, which are activated by [...] Read more.
Angiotensin II receptor type 1 (AT1R) and endothelin-1 receptor type A (ETAR) are G-protein-coupled receptors (GPCRs) expressed on the surface of a great variety of cells: immune cells, vascular smooth cells, endothelial cells, and fibroblasts express ETAR and AT1R, which are activated by endothelin 1 (ET1) and angiotensin II (AngII), respectively. Certain autoantibodies are specific for these receptors and can regulate their function, thus being known as functional autoantibodies. The function of these antibodies is similar to that of natural ligands, and it involves not only vasoconstriction, but also the secretion of proinflammatory cytokines (such as interleukin-6 (IL6), IL8 and TNF-α), collagen production by fibroblasts, and reactive oxygen species (ROS) release by fibroblasts and neutrophils. The role of autoantibodies against AT1R and ETAR (AT1R-AAs and ETAR-AAs, respectively) is well described in the pathogenesis of many medical conditions (e.g., systemic sclerosis (SSc) and SSc-associated pulmonary hypertension, cystic fibrosis, and allograft dysfunction), but their implications in cardiovascular diseases are still unclear. This review summarizes the current evidence regarding the effects of AT1R-AAs and ETAR-AAs in cardiovascular pathologies, highlighting their roles in heart transplantation and mechanical circulatory support, preeclampsia, and acute coronary syndromes. Full article
(This article belongs to the Special Issue Old and New Players in Inflammatory Disorders—in Memory of Dr. Nadia Ferlazzo)
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