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Functional Role of Cytokines in Cancer and Chronic Inflammation

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

Deadline for manuscript submissions: 31 August 2024 | Viewed by 6522

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Special Issue Editors

Dr. Elizaveta Fasler-Kan

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Guest Editor

1. Department of Pediatric Surgery, Children's Hospital Inselspital, University of Bern, Freiburgstrasse 15, CH-3010 Bern, Switzerland
2. Department of Biomedical Research, University of Bern, Freiburgstrasse 15, CH-3010 Bern, Switzerland
Interests: cytokines; signaling pathway; checkpoint proteins; tumour biology

Dr. Daria M. Potashnikova

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Guest Editor

1. City Clinical Hospital Named After I.V. Davydovsky, Moscow Department of Healthcare, Moscow, Russia
2. Ministry of Healthcare, A.I. Yevdokimov Moscow State University of Medicine and Dentistry of the Ministry of Healthcare of the Russian Federation, Moscow, Russia
3. Department of Cell Biology and Histology, School of Biology, Lomonosov Moscow State University, Moscow, Russia
Interests: cytokines; inflammation; immune cells; cell migration; atherosclerosis

Special Issue Information

Dear Colleagues,

Cytokines form a diverse group of signaling proteins which are secreted by a wide range of cell types, including immunocompetent cells, and contribute to various aspects of inflammation, such as cell damage, metabolic alterations, angiogenesis, cell haemoattraction and migration. Beyond their more apparent role in acute inflammation, these molecules are responsible for a longstanding and less-studied chronic inflammatory response that is now known to drive a number of diseases, most notably a wide range of cancers, cardiovascular disease, and autoimmune and neurodegenerative disorders. Cytokines, which are involved in chronic inflammation, have specific effects on the cross-talk between various cell types and thus form a microenvironment that can either promote or block disease progression.

Over the last 30 years, the role of cytokines and their receptors have been extensively investigated in both cancer progression and anti-cancer therapy. However, more effective immunotherapies require the cytokine profiling of each tumour type and comprehensive understanding of tumour biology. In cardiovascular disease, cytokines are an important part of the atherogenic environment and thus appear as potential targets in atherosclerosis prevention and treatment.

The articles published in this Special Issue will cover all aspects of fundamental and translational cytokine research for better understanding of cancer development and chronic inflammation-related diseases. This includes pathogenesis, progression and cytokine-specific therapeutic approaches.

Dr. Elizaveta Fasler-Kan
Dr. Daria M. Potashnikova
Guest Editors

Manuscript Submission Information

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Keywords

cytokines
interleukins
cytokine antagonists
signaling pathways
chronic inflammation
immunometabolism
cancer development
cancer progression
immunotherapy
cytokine therapy

Published Papers (6 papers)

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Research

13 pages, 1861 KiB

Open AccessArticle

The Differential Effect of Senolytics on SASP Cytokine Secretion and Regulation of EMT by CAFs

by Daria A. Bogdanova, Ekaterina D. Kolosova, Tamara V. Pukhalskaia, Ksenia A. Levchuk, Oleg N. Demidov and Ekaterina V. Belotserkovskaya

Int. J. Mol. Sci. 2024, 25(7), 4031; https://doi.org/10.3390/ijms25074031 - 04 Apr 2024

Viewed by 508

Abstract

The tumor microenvironment (TME) plays an essential role in tumor progression and in modulating tumor response to anticancer therapy. Cellular senescence leads to a switch in the cell secretome, characterized by the senescence-associated secretory phenotype (SASP), which may regulate tumorigenesis. Senolytic therapy is considered a novel anticancer strategy that eliminates the deleterious effects of senescent cells in the TME. Here, we show that two different types of senolytic drugs, despite efficiently depleting senescent cells, have opposite effects on cancer-associated fibroblasts (CAFs) and their ability to regulate epithelial–mesenchymal transition (EMT). We found that senolytic drugs, navitoclax and the combination of dasatinib/quercetin, reduced the number of spontaneously senescent and TNF-induced senescent CAFs. Despite the depletion of senescent cells, the combination of dasatinib/quercetin versus navitoclax increased the secretion of the SASP pro-inflammatory cytokine IL-6. This differential effect correlated with the promotion of enhanced migration and EMT in MC38 colorectal cancer cells. Our results demonstrate that some senolytics may have side effects unrelated to their senolytic activity and may promote tumorigenesis. We argue for more careful and extensive studies of the effects of senolytics on various aspects of tumor progression and tumor resistance to therapy before the senolytic strategy is implemented in the clinic. Full article

(This article belongs to the Special Issue Functional Role of Cytokines in Cancer and Chronic Inflammation)

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14 pages, 2086 KiB

Open AccessArticle

Cytokine Signaling in Pediatric Kidney Tumor Cell Lines WT-CLS1, WT-3ab and G-401

by Elizaveta Fasler-Kan, Milan Milošević, Sabrina Ruggiero, Nijas Aliu, Dietmar Cholewa, Frank-Martin Häcker, Gabriela Dekany, Andreas Bartenstein and Steffen M. Berger

Int. J. Mol. Sci. 2024, 25(4), 2281; https://doi.org/10.3390/ijms25042281 - 14 Feb 2024

Viewed by 818

Abstract

Renal tumors comprise ~7% of all malignant pediatric tumors. Approximately 90% of pediatric kidney tumors comprise Wilms tumors, and the remaining 10% include clear cell sarcoma of the kidney, malignant rhabdoid tumor of the kidney, renal cell carcinoma and other rare renal tumors. Over the last 30 years, the role of cytokines and their receptors has been considerably investigated in both cancer progression and anti-cancer therapy. However, more effective immunotherapies require the cytokine profiling of each tumor type and comprehensive understanding of tumor biology. In this study, we aimed to investigate the activation of signaling pathways in response to cytokines in three pediatric kidney tumor cell lines, in WT-CLS1 and WT-3ab cells (both are Wilms tumors), and in G-401 cells (a rhabdoid kidney tumor, formerly classified as Wilms tumor). We observed that interferon-alpha (IFN-α) and interferon-gamma (IFN-γ) very strongly induced the activation of the STAT1 protein, whereas IL-6 and IFN-α activated STAT3 and IL-4 activated STAT6 in all examined tumor cell lines. STAT protein activation was examined by flow cytometry and Western blot using phospho-specific anti-STAT antibodies which recognize only activated (phosphorylated) STAT proteins. Nuclear translocation of phospho-STAT proteins upon activation with specific cytokines was furthermore confirmed by immunofluorescence. Our results also showed that both IFN-α and IFN-γ caused upregulation of major histocompatibility complex (MHC) class I proteins, however, these cytokines did not have any effect on the expression of MHC class II proteins. We also observed that pediatric kidney tumor cell lines exhibit the functional expression of an additional cytokine signaling pathway, the tumor necrosis factor (TNF)-α-mediated activation of nuclear factor kappa B (NF-κB). In summary, our data show that human pediatric renal tumor cell lines are responsive to stimulation with various human cytokines and could be used as in vitro models for profiling cytokine signaling pathways. Full article

(This article belongs to the Special Issue Functional Role of Cytokines in Cancer and Chronic Inflammation)

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24 pages, 10559 KiB

Open AccessArticle

Cytokine Profiling of Plasma and Atherosclerotic Plaques in Patients Undergoing Carotid Endarterectomy

by Daria Potashnikova, Elena Maryukhnich, Daria Vorobyeva, George Rusakovich, Alexey Komissarov, Anna Tvorogova, Vladimir Gontarenko and Elena Vasilieva

Int. J. Mol. Sci. 2024, 25(2), 1030; https://doi.org/10.3390/ijms25021030 - 14 Jan 2024

Viewed by 944

Abstract

Atherosclerotic plaques are sites of chronic inflammation with diverse cell contents and complex immune signaling. Plaque progression and destabilization are driven by the infiltration of immune cells and the cytokines that mediate their interactions. Here, we attempted to compare the systemic cytokine profiles in the blood plasma of patients with atherosclerosis and the local cytokine production, using ex vivo plaque explants from the same patients. The developed method of 41-plex xMAP data normalization allowed us to differentiate twenty-two cytokines produced by the plaque that were not readily detectable in free circulation and six cytokines elevated in blood plasma that may have other sources than atherosclerotic plaque. To verify the xMAP data on the putative atherogenesis-driving chemokines MCP-1 (CCL2), MIP-1α (CCL3), MIP-1β (CCL4), RANTES (CCL5), and fractalkine (CX3CL1), qPCR was performed. The MIP1A (CCL3), MIP1B (CCL4), FKN (CX3CL1), and MCP1 (CCL2) genes were expressed at high levels in the plaques, whereas RANTES (CCL5) was almost absent. The expression patterns of the chemokines were restricted to the plaque cell types: the MCP1 (CCL2) gene was predominantly expressed in endothelial cells and monocytes/macrophages, MIP1A (CCL3) in monocytes/macrophages, and MIP1B (CCL4) in monocytes/macrophages and T cells. RANTES (CCL5) was restricted to T cells, while FKN (CX3CL1) was not differentially expressed. Taken together, our data indicate a plaque-specific cytokine production profile that may be a useful tool in atherosclerosis studies. Full article

(This article belongs to the Special Issue Functional Role of Cytokines in Cancer and Chronic Inflammation)

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15 pages, 3980 KiB

Open AccessArticle

by Ryeonshi Kang, Charlotte Laborde, Lesia Savchenko, Audrey Swiader, Nathalie Pizzinat, Dimitri Marsal, Yannis Sainte-Marie, Frederic Boal, Helene Tronchere, Jerome Roncalli and Oksana Kunduzova

Int. J. Mol. Sci. 2023, 24(21), 15841; https://doi.org/10.3390/ijms242115841 - 31 Oct 2023

Viewed by 1040

Abstract

Age-related alterations in cardiac function, metabolic, inflammatory and antioxidant profiles are associated with an increased risk of cardiovascular mortality and morbidity. Here, we examined cardiac and metabolic phenotypes in relation to inflammatory status and antioxidant capacity in young, middle-aged and old mice. Real-time reverse transcription–polymerase chain reactions were performed on myocardium and immunoassays on plasma. Left ventricular (LV) structure and function were assessed by echocardiography using high-frequency ultrasound. Middle-aged mice exhibited an altered metabolic profile and antioxidant capacity compared to young mice, whereas myocardial expression of inflammatory factors (TNFα, IL1β, IL6 and IL10) remained unchanged. In contrast, old mice exhibited increased expression of inflammatory cytokines and plasma levels of resistin compared to young and middle-aged mice (p < 0.05). The pro-inflammatory signature of aged hearts was associated with alterations in glutathione redox homeostasis and elevated contents of 4-hydroxynonenal (4-HNE), a marker of lipid peroxidation and oxidative stress. Furthermore, echocardiographic parameters of LV systolic and diastolic functions were significantly altered in old mice compared to young mice. Taken together, these findings suggest age-related shifts in cardiac phenotype encompass the spectrum of metabo-inflammatory abnormalities and altered redox homeostasis. Full article

(This article belongs to the Special Issue Functional Role of Cytokines in Cancer and Chronic Inflammation)

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21 pages, 4449 KiB

Open AccessArticle

High and Low Levels of ABCB1 Expression Are Associated with Two Distinct Gene Signatures in Lung Tissue of Pulmonary TB Patients with High Inflammation Activity

by Ekaterina N. Pavlova, Larisa N. Lepekha, Ekaterina Yu. Rybalkina, Ruslan V. Tarasov, Ksenia A. Sychevskaya, Elena E. Voronezhskaya, Alexander G. Masyutin, Atadzhan E. Ergeshov and Maria V. Erokhina

Int. J. Mol. Sci. 2023, 24(19), 14839; https://doi.org/10.3390/ijms241914839 - 02 Oct 2023

Viewed by 1172

Abstract

P-glycoprotein (encoded by the ABCB1 gene) has a dual role in regulating inflammation and reducing chemotherapy efficacy in various diseases, but there are few studies focused on pulmonary TB patients. In this study, our objective was to identify a list of genes that correlate with high and low levels of ABCB1 gene expression in the lungs of pulmonary TB patients with different activity of chronic granulomatous inflammation. We compared gene expression in two groups of samples (with moderate and high activity of tuberculomas) to identify their characteristic gene signatures. Gene expression levels were determined using quantitative PCR in samples of perifocal area of granulomas, which were obtained from 65 patients after surgical intervention. Subsequently, two distinct gene signatures associated with high inflammation activity were identified. The first signature demonstrated increased expression of HIF1a, TGM2, IL6, SOCS3, and STAT3, which correlated with high ABCB1 expression. The second signature was characterized by high expression of TNFa and CD163 and low expression of ABCB1. These results provide insight into various inflammatory mechanisms and association with P-gp gene expression in lung tissue of pulmonary TB patients and will be useful in the development of a host-directed therapy approach to improving the effectiveness of anti-TB treatment. Full article

(This article belongs to the Special Issue Functional Role of Cytokines in Cancer and Chronic Inflammation)

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11 pages, 1975 KiB

Open AccessArticle

Metabolic, Apoptotic and Fibro-Inflammatory Profiles of the Heart Exposed to Environmental Electromagnetic Fields

by Lesia Savchenko, Ilenia Martinelli, Dimitri Marsal, Oksana Batkivska, Vyacheslav Zhdan, Igor Kaidashev, Nathalie Pizzinat, Frederic Boal, Helene Tronchere, Junwu Tao and Oksana Kunduzova

Int. J. Mol. Sci. 2023, 24(14), 11709; https://doi.org/10.3390/ijms241411709 - 20 Jul 2023

Viewed by 1152

Abstract

Environmental stress can disturb the integrative functioning of the cardiovascular system and trigger a number of adaptive and/or maladaptive cell responses. Concomitant with the expanding use of mobile communication systems, public exposure to electromagnetic fields (EMFs) raises the question of the impact of 900 MHz EMFs on cardiovascular health. Therefore, in this study, we experimentally investigated whether 915 MHz EMF exposure influenced cardiac metabolic, antioxidant, apoptotic, and fibro-inflammatory profiles in a mouse model. Healthy mice were sham-exposed or exposed to EMF for 14 days. Western blot analysis using whole cardiac tissue lysates demonstrated that there was no significant change in the expression of oxidative phosphorylation (OXPHOS) complexes between the control and EMF-exposed mice. In addition, the myocardial expression of fibro-inflammatory cytokines, antioxidant enzymes, and apoptosis-related markers remained unchanged in the EMF-challenged hearts. Finally, the structural integrity of the cardiac tissues was preserved among the groups. These findings suggest that the apoptotic, antioxidant, metabolic, and fibro-inflammatory profiles of the heart remained stable under conditions of EMF exposure in the analyzed mice. Full article

(This article belongs to the Special Issue Functional Role of Cytokines in Cancer and Chronic Inflammation)

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