Inflammation in Target Organs

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Immunology".

Deadline for manuscript submissions: 15 July 2025 | Viewed by 9490

Special Issue Editors


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Guest Editor
Diabetes Unit, Department of Endocrinology and Metabolism, Hadassah Medical Center, The Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 91120, Israel
Interests: insulin resistance; diabetes; lipid metabolism; glucose metabolism; disease prevention; obesity metabolic endocrinology; high fructose corn syrup; cardiovascular disease; obesity; telemedicine; telehealth; eHealth; mHealth; digital health; review; connected diabetes care; diabetes mellitus; glucose monitoring
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Guest Editor Assistant
Goldman Medical School, Faculty of Health Sciences, Ben Gurion University, Beer Sheva 8410501, Israel
Interests: diabetes; obesity
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Special Issue Information

Dear Colleagues,

Various metabolic disorders affect target organs, such as the heart, kidneys, liver, blood vessels, and the brain. A substantial portion of the resultant damage can be attributed to inflammatory processes, compromising the functionality of these organs. Inflammation may induce organ fibrosis and precipitate irreversible damage. In this Special Issue, we will present an overview elucidating the inflammatory response, resultant damage, and future therapies to prevent and cure inflammation in target organs. We will explore the intricate relationship between inflammation and organ damage, drawing insights from studies on cell lines, animal models, and humans.

This Special Issue endeavors to underscore recent discoveries, elucidating the intricate mechanisms through which inflammation inflicts damage on the target organs. Its objective is to offer a comprehensive scope, encompassing research papers and reviews delineating specific interactions between target organs and inflammation. Such discernments possess the potential to profoundly shape future therapeutic strategies within this domain of study.

Prof. Dr. Itamar Raz
Guest Editor

Roni Weinberg Sibony
Guest Editor Assistant

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Keywords

  • inflammation
  • fibrosis
  • cardio-renal
  • vascular
  • liver
  • brain

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Published Papers (5 papers)

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Research

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30 pages, 2647 KiB  
Article
Renal Inflammation, Oxidative Stress, and Metabolic Abnormalities During the Initial Stages of Hypertension in Spontaneously Hypertensive Rats
by Paweł Wojtacha, Ewelina Bogdańska-Chomczyk, Mariusz Krzysztof Majewski, Kazimierz Obremski, Michał Stanisław Majewski and Anna Kozłowska
Cells 2024, 13(21), 1771; https://doi.org/10.3390/cells13211771 - 25 Oct 2024
Viewed by 1241
Abstract
Background: Hypertension is a major cause of mortality worldwide. The kidneys play a crucial role in regulating blood pressure and fluid volume. The relationship between the kidneys and hypertension is complex, involving factors such as the renin–angiotensin system, oxidative stress, and inflammation. This [...] Read more.
Background: Hypertension is a major cause of mortality worldwide. The kidneys play a crucial role in regulating blood pressure and fluid volume. The relationship between the kidneys and hypertension is complex, involving factors such as the renin–angiotensin system, oxidative stress, and inflammation. This study aims to assess the levels of inflammatory markers, oxidative stress, and metabolic factors in the kidneys, focusing on their potential role in early renal damage and their association with the development of hypertension. Methods: This study was designed to compare the levels of selected inflammatory markers, e.g., interleukins, tumor necrosis factor-α (TNF-α), transforming growth factor, and serine/threonine-protein (mTOR); oxidative stress markers such as malondialdehyde, sulfhydryl group, and glucose (GLC); and metabolic markers among other enzymes, such as alanine transaminase (ALT), aspartate transaminase (AST), hexokinase II (HK-II), and hypoxia-inducible factor-1α (HIF-1α), as well as creatinine in the kidneys of spontaneously hypertensive rats (SHR/NCrl, n = 12) and Wistar Kyoto rats (WKY/NCrl, n = 12). Both juvenile (5 weeks old) and maturing (10 weeks old) specimens were examined using spectrophotometric methods, e.g., ELISA. Results: Juvenile SHRs exhibited reduced renal levels of all studied cytokines and chemokines, with lower oxidative stress and deficits in the mTOR and HK-II levels compared to the age-matched WKYs. Maturing SHRs showed increased renal levels of interleukin-1β (IL-1β), IL-6, IL-18, and TNF-α, alongside elevated carbonyl stress and increased HIF-1α as opposed to their control peers. The levels of all other studied markers were normalized in these animals, except for ALT (increased), ALP, and GLC (both reduced). Conclusions: This study underscores the significant impact of inflammatory, oxidative stress, and metabolic marker changes on renal function. Juvenile SHRs display lower marker levels, indicating an immature immune response and potential subclinical kidney damage that may contribute to hypertension development. In contrast, mature SHRs exhibit chronic inflammation, oxidative dysregulation, and metabolic disturbances, suggesting cellular damage. These changes create a feedback loop that worsens kidney function and accelerates hypertension progression, highlighting the kidneys’ crucial role in both initiating and exacerbating this condition. Full article
(This article belongs to the Special Issue Inflammation in Target Organs)
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16 pages, 4382 KiB  
Article
Combined Insults of a MASH Diet and Alcohol Binges Activate Intercellular Communication and Neutrophil Recruitment via the NLRP3-IL-1β Axis in the Liver
by Mrigya Babuta, Prashanth Thevkar Nagesh, Aditi Ashish Datta, Victoria Remotti, Yuan Zhuang, Jeeval Mehta, Francesca Lami, Yanbo Wang and Gyongyi Szabo
Cells 2024, 13(11), 960; https://doi.org/10.3390/cells13110960 - 1 Jun 2024
Cited by 5 | Viewed by 1780
Abstract
Binge drinking in obese patients positively correlates with accelerated liver damage and liver-related death. However, the underlying mechanism and the effect of alcohol use on the progression of metabolic-dysfunction-associated steatotic liver disease (MASLD) remain unexplored. Here, we show that short-term feeding of a [...] Read more.
Binge drinking in obese patients positively correlates with accelerated liver damage and liver-related death. However, the underlying mechanism and the effect of alcohol use on the progression of metabolic-dysfunction-associated steatotic liver disease (MASLD) remain unexplored. Here, we show that short-term feeding of a metabolic-dysfunction-associated steatohepatitis (MASH) diet plus daily acute alcohol binges for three days induce liver injury and activation of the NLRP3 inflammasome. We identify that a MASH diet plus acute alcohol binges promote liver inflammation via increased infiltration of monocyte-derived macrophages, neutrophil recruitment, and NET release in the liver. Our results suggest that both monocyte-derived macrophages and neutrophils are activated via NLRP3, while the administration of MCC950, an NLRP3 inhibitor, dampens these effects.In this study, we reveal important intercellular communication between hepatocytes and neutrophils. We discover that the MASH diet plus alcohol induces IL-1β via NLRP3 activation and that IL-1β acts on hepatocytes and promotes the production of CXCL1 and LCN2. In turn, the increase in these neutrophils recruits chemokines and causes further infiltration and activation of neutrophils in the liver. In vivo administration of the NLRP3 inhibitor, MCC950, improves the early phase of MetALD by preventing liver damage, steatosis, inflammation, and immune cells recruitment. Full article
(This article belongs to the Special Issue Inflammation in Target Organs)
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20 pages, 10992 KiB  
Article
Investigation into Cardiac Myhc-α 334–352-Specific TCR Transgenic Mice Reveals a Role for Cytotoxic CD4 T Cells in the Development of Cardiac Autoimmunity
by Meghna Sur, Mahima T. Rasquinha, Kiruthiga Mone, Chandirasegaran Massilamany, Ninaad Lasrado, Channabasavaiah Gurumurthy, Raymond A. Sobel and Jay Reddy
Cells 2024, 13(3), 234; https://doi.org/10.3390/cells13030234 - 26 Jan 2024
Cited by 2 | Viewed by 2608
Abstract
Myocarditis is one of the major causes of heart failure in children and young adults and can lead to dilated cardiomyopathy. Lymphocytic myocarditis could result from autoreactive CD4+ and CD8+ T cells, but defining antigen specificity in disease pathogenesis is challenging. [...] Read more.
Myocarditis is one of the major causes of heart failure in children and young adults and can lead to dilated cardiomyopathy. Lymphocytic myocarditis could result from autoreactive CD4+ and CD8+ T cells, but defining antigen specificity in disease pathogenesis is challenging. To address this issue, we generated T cell receptor (TCR) transgenic (Tg) C57BL/6J mice specific to cardiac myosin heavy chain (Myhc)-α 334–352 and found that Myhc-α-specific TCRs were expressed in both CD4+ and CD8+ T cells. To investigate if the phenotype is more pronounced in a myocarditis-susceptible genetic background, we backcrossed with A/J mice. At the fourth generation of backcrossing, we observed that Tg T cells from naïve mice responded to Myhc-α 334–352, as evaluated by proliferation assay and carboxyfluorescein succinimidyl ester staining. The T cell responses included significant production of mainly pro-inflammatory cytokines, namely interferon (IFN)-γ, interleukin-17, and granulocyte macrophage-colony stimulating factor. While the naïve Tg mice had isolated myocardial lesions, immunization with Myhc-α 334–352 led to mild myocarditis, suggesting that further backcrossing to increase the percentage of A/J genome close to 99.99% might show a more severe disease phenotype. Further investigations led us to note that CD4+ T cells displayed the phenotype of cytotoxic T cells (CTLs) akin to those of conventional CD8+ CTLs, as determined by the expression of CD107a, IFN-γ, granzyme B natural killer cell receptor (NKG)2A, NKG2D, cytotoxic and regulatory T cell molecules, and eomesodermin. Taken together, the transgenic system described in this report may be a helpful tool to distinguish the roles of cytotoxic cardiac antigen-specific CD4+ T cells vs. those of CD8+ T cells in the pathogenesis of myocarditis. Full article
(This article belongs to the Special Issue Inflammation in Target Organs)
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Review

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23 pages, 1147 KiB  
Review
Inflammatory Pathways in Coronary Artery Disease: Which Ones to Target for Secondary Prevention?
by Wan-Hei Cheng and Ying Wang
Cells 2025, 14(3), 153; https://doi.org/10.3390/cells14030153 - 21 Jan 2025
Viewed by 585
Abstract
Coronary artery disease (CAD), the build-up of atherosclerotic plaques on the wall of blood vessels, causes adverse cardiovascular events. Secondary prevention focuses on treating patients with existing plaques to prevent disease progression. Recent studies have shown that inflammation is an independent risk factor [...] Read more.
Coronary artery disease (CAD), the build-up of atherosclerotic plaques on the wall of blood vessels, causes adverse cardiovascular events. Secondary prevention focuses on treating patients with existing plaques to prevent disease progression. Recent studies have shown that inflammation is an independent risk factor that drives disease progression, and targeting inflammation could be an effective therapeutic strategy for secondary prevention. In this review, we highlighted the roles of several inflammatory pathways in rupture and erosion, two major processes through which established plaques lead to adverse cardiovascular events. In the past 15 years, numerous clinical trials have tested the therapeutic potential of targeting these pathways, including neutralizing inflammatory cytokines and blocking signaling transduction of the inflammatory pathways. Only colchicine was approved for clinical use in patients with CAD. This is primarily due to the multifaceted roles of inflammatory pathways in disease progression. Commonly used pre-clinical models provided robust information for the onset of early disease but limited understanding of the inflammatory network in established plaques. This review will summarize lessons learned from successful and failed clinical trials to advocate for assessing inflammation in established plaques before designing therapeutics for secondary prevention. Full article
(This article belongs to the Special Issue Inflammation in Target Organs)
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22 pages, 1312 KiB  
Review
Inflammatory Trajectory of Type 2 Diabetes: Novel Opportunities for Early and Late Treatment
by Valeria Pellegrini, Rosalba La Grotta, Francesca Carreras, Angelica Giuliani, Jacopo Sabbatinelli, Fabiola Olivieri, Cesare Celeste Berra, Antonio Ceriello and Francesco Prattichizzo
Cells 2024, 13(19), 1662; https://doi.org/10.3390/cells13191662 - 8 Oct 2024
Cited by 3 | Viewed by 2597
Abstract
Low-grade inflammation (LGI) represents a key driver of type 2 diabetes (T2D) and its associated cardiovascular diseases (CVDs). Indeed, inflammatory markers such as hs-CRP and IL-6 predict the development of T2D and its complications, suggesting that LGI already increases before T2D diagnosis and [...] Read more.
Low-grade inflammation (LGI) represents a key driver of type 2 diabetes (T2D) and its associated cardiovascular diseases (CVDs). Indeed, inflammatory markers such as hs-CRP and IL-6 predict the development of T2D and its complications, suggesting that LGI already increases before T2D diagnosis and remains elevated even after treatment. Overnutrition, unhealthy diets, physical inactivity, obesity, and aging are all recognized triggers of LGI, promoting insulin resistance and sustaining the pathogenesis of T2D. Once developed, and even before frank appearance, people with T2D undergo a pathological metabolic remodeling, with an alteration of multiple CVD risk factors, i.e., glycemia, lipids, blood pressure, and renal function. In turn, such variables foster a range of inflammatory pathways and mechanisms, e.g., immune cell stimulation, the accrual of senescent cells, long-lasting epigenetic changes, and trained immunity, which are held to chronically fuel LGI at the systemic and tissue levels. Targeting of CVD risk factors partially ameliorates LGI. However, some long-lasting inflammatory pathways are unaffected by common therapies, and LGI burden is still increased in many T2D patients, a phenomenon possibly underlying the residual inflammatory risk (i.e., having hs-CRP > 2 mg/dL despite optimal LDL cholesterol control). On the other hand, selected disease-modifying drugs, e.g., GLP-1RA, seem to also act on the pathogenesis of T2D, curbing the inflammatory trajectory of the disease and possibly preventing it if introduced early. In addition, selected trials demonstrated the potential of canonical anti-inflammatory therapies in reducing the rate of CVDs in patients with this condition or at high risk for it, many of whom had T2D. Since colchicine, an inhibitor of immune cell activation, is now approved for the prevention of CVDs, it might be worth exploring a possible therapeutic paradigm to identify subjects with T2D and an increased LGI burden to treat them with this drug. Upcoming studies will reveal whether disease-modifying drugs reverse early T2D by suppressing sources of LGI and whether colchicine has a broad benefit in people with this condition. Full article
(This article belongs to the Special Issue Inflammation in Target Organs)
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