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Article ; Online: Sphingosine-1-Phosphate Shapes Healthy Monocytes into An Immunosuppressive Phenotype.

Terlizzi, Michela / Falanga, Anna / Colarusso, Chiara / Pinto, Aldo / Sorrentino, Rosalinda

Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology

2024 Volume 58, Issue 2, Page(s) 156–171

Abstract: Background/aims: The physiological phenotype of individuals can influence and shape real-life phenomena in that it can contribute to the development of specific characteristics that can affect the immune response to specific stimuli. In this study we ... ...

Abstract	Background/aims: The physiological phenotype of individuals can influence and shape real-life phenomena in that it can contribute to the development of specific characteristics that can affect the immune response to specific stimuli. In this study we aimed to understand whether the sphingosine/sphingosine-1-phoshate (S1P) axis can modulate the immunotype of circulating cells. Methods: To pursue this goal, we performed bioinformatic analyses of public datasets. Results: The transcriptomic profile of healthy subjects of GSE192829 dataset identified two clusters with different transcriptional repertoire. Cluster 1 expressed higher levels of enzymes for S1P formation than cluster 0 which was characterized by enzymes that lead to ceramide formation, which represent the opposite metabolic direction. Inference analysis showed that cluster 1 was higher populated by monocytes, CD4 Conclusion: In conclusion this study highlights that S1P-associated hub markers can be useful to discriminate subjects with pronounced immunosuppression.
MeSH term(s)	Humans ; Sphingosine/metabolism ; Sphingosine/analogs & derivatives ; Monocytes/metabolism ; Lysophospholipids/metabolism ; Immunosuppressive Agents ; Phenotype
Chemical Substances	sphingosine 1-phosphate (26993-30-6) ; Sphingosine (NGZ37HRE42) ; Lysophospholipids ; Immunosuppressive Agents
Language	English
Publishing date	2024-04-18
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1067572-3
ISSN	1421-9778 ; 1015-8987
ISSN (online)	1421-9778
ISSN	1015-8987
DOI	10.33594/000000691
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Article ; Online: The activation of the AIM2 inflammasome after cigarette smoke exposure leads to an immunosuppressive lung microenvironment.

Colarusso, Chiara / Falanga, Anna / Di Caprio, Simone / Terlizzi, Michela / Pinto, Aldo / Maiolino, Piera / Sorrentino, Rosalinda

International immunopharmacology

2024 Volume 131, Page(s) 111832

Abstract: Cigarette smoke is widely known as contributing to chronic inflammation underlying several airway diseases, such as chronic obstructive pulmonary disease (COPD) and lung cancer. In our previous studies we found that the lung of both COPD and cancer ... ...

Abstract	Cigarette smoke is widely known as contributing to chronic inflammation underlying several airway diseases, such as chronic obstructive pulmonary disease (COPD) and lung cancer. In our previous studies we found that the lung of both COPD and cancer patients were characterized by the presence and activation of the AIM2 inflammasome. Here, we wanted to investigate the upstream step during the establishment of chronic lung inflammation after cigarette smoke exposure. We took advantage of a mouse model of smoking exposure and public scRNAseq data. We found that AIM2 mRNA was expressed in both alveolar type II, B cells, T regulatory (Treg) and macrophages detected in the lung of non-smokers (n = 4) and smokers (n = 3). The activation of AIM2 in smoking mice by using PolydA:dT did not alter cigarette-smoke-induced alveoli enlargement and mucus production, rather it induced higher recruitment of immunosuppressive cells, such as non-active dendritic cells (DCs), Arginase I+ macrophages, myeloid-derived suppressor cells (MDSC) and Tregs. In addition, the inflammatory environment after AIM2 activation in smoking mice was characterized by higher levels of IL-1α, IL-1β, IL-33, TNFα, LDH, IL-10 and TGFβ. This scenario was not altered after the pharmacological inhibition of both caspase-1 and STING pathway. In conclusion, these data suggest that chronic inflammation after cigarette smoke exposure is associated with AIM2 activation, which could lead towards cigarette smoke-associated lung diseases.
MeSH term(s)	Animals ; Humans ; Mice ; Cigarette Smoking/adverse effects ; DNA-Binding Proteins/genetics ; Inflammasomes/metabolism ; Inflammation ; Lung/metabolism ; Mice, Inbred C57BL ; Pulmonary Disease, Chronic Obstructive
Chemical Substances	AIM2 protein, human ; DNA-Binding Proteins ; Inflammasomes
Language	English
Publishing date	2024-03-10
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2043785-7
ISSN	1878-1705 ; 1567-5769
ISSN (online)	1878-1705
ISSN	1567-5769
DOI	10.1016/j.intimp.2024.111832
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Article ; Online: A lesson from a saboteur: High-MW kininogen impact in coronavirus-induced disease 2019.

Colarusso, Chiara / Terlizzi, Michela / Pinto, Aldo / Sorrentino, Rosalinda

British journal of pharmacology

2020 Volume 177, Issue 21, Page(s) 4866–4872

Abstract: The newly identified coronavirus SARS-CoV-2 that spread from China is causing the pandemic COVID-19 with a fatality rate from 5-15%. It causes fever, cough, myalgia, fatigue up to dyspnoea, responsible for hospitalization and artificial oxygenation. SARS- ...

Abstract	The newly identified coronavirus SARS-CoV-2 that spread from China is causing the pandemic COVID-19 with a fatality rate from 5-15%. It causes fever, cough, myalgia, fatigue up to dyspnoea, responsible for hospitalization and artificial oxygenation. SARS-CoV-2 infects human cells using ACE2, the transmembrane protease serine 2 (TMPRSS2) and the SARS-CoV-2 main protease (M
MeSH term(s)	Antibodies, Monoclonal, Humanized/administration & dosage ; Antibodies, Monoclonal, Humanized/pharmacology ; Betacoronavirus/isolation & purification ; COVID-19 ; Coronavirus Infections/drug therapy ; Coronavirus Infections/virology ; Humans ; Kallikrein-Kinin System/drug effects ; Kininogen, High-Molecular-Weight/metabolism ; Pandemics ; Pneumonia, Viral/drug therapy ; Pneumonia, Viral/virology ; SARS-CoV-2
Chemical Substances	Antibodies, Monoclonal, Humanized ; Kininogen, High-Molecular-Weight ; lanadelumab (2372V1TKXK)
Keywords	covid19
Language	English
Publishing date	2020-06-30
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	80081-8
ISSN	1476-5381 ; 0007-1188
ISSN (online)	1476-5381
ISSN	0007-1188
DOI	10.1111/bph.15154
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Article ; Online: Induction of Inflammation Disrupts the Negative Interplay between STING and S1P Axis That Is Observed during Physiological Conditions in the Lung.

Terlizzi, Michela / Colarusso, Chiara / Falanga, Anna / Somma, Pasquale / De Rosa, Ilaria / Panico, Luigi / Pinto, Aldo / Maiolino, Piera / Sorrentino, Rosalinda

International journal of molecular sciences

2023 Volume 24, Issue 9

Abstract: The stimulator of interferon genes (STING) is a master regulator of innate immunity, involved in several inflammatory diseases. Our previous data showed that sphingosine-1-phosphate (S1P) is released during inflammatory conditions in the lung. The aim of ...

Abstract	The stimulator of interferon genes (STING) is a master regulator of innate immunity, involved in several inflammatory diseases. Our previous data showed that sphingosine-1-phosphate (S1P) is released during inflammatory conditions in the lung. The aim of this study was to understand the interplay between S1P and STING during both physiological and pathological conditions. The mRNA levels of ceramidase (ASAH1), S1P precursor enzyme, and STING were inversely correlated in healthy lung tissues, but positively correlated in tumor tissues. The activation of STING induced higher expression of ASAH1 and was accompanied by IFN-β and IL-6 release. ASAH1 and sphingosine kinases (SPHK I/II) blockade significantly reduced IL-6, but not IFNβ, after STING activation. In support of this, taking advantage of a mouse model, we found that inflamed lungs had higher levels of inactive ASAH1 when STING was inhibited. This confirmed the human data, where higher levels of STING promoted the activation of ASAH1. Lung cancer patients positive to STING and ASAH1 mRNA levels had a dismal prognosis in that the overall survival was reduced compared to STING/ASAH1 negative patients. These data highlight that during physiological conditions, STING and the S1P axis do not interfere, whereas in lung cancer patients their interplay is associated to poor prognosis.
MeSH term(s)	Animals ; Humans ; Mice ; Inflammation ; Interleukin-6/genetics ; Lung/metabolism ; Lung Neoplasms/genetics ; Lysophospholipids/metabolism ; Sphingosine/metabolism
Chemical Substances	Interleukin-6 ; Lysophospholipids ; Sphingosine (NGZ37HRE42) ; sphingosine 1-phosphate (26993-30-6) ; STING1 protein, human ; Sting1 protein, mouse
Language	English
Publishing date	2023-05-05
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24098303
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Article ; Online: Absent in melanoma 2 (AIM2) positive profile identifies a poor prognosis of lung adenocarcinoma patients.

Colarusso, Chiara / Terlizzi, Michela / Falanga, Anna / Stathopoulos, Georgious / De Lucia, Luigi / Hansbro, Phillip M / Pinto, Aldo / Sorrentino, Rosalinda

International immunopharmacology

2023 Volume 124, Issue Pt B, Page(s) 110990

Abstract: The absent in melanoma 2 (AIM2) inflammasome has been demonstrated as involved in tumor growth. In this study we used human samples of lung adenocarcinoma (LUAD) patients, taking advantage of a mouse model of smoking cessation. Human samples were ... ...

Abstract	The absent in melanoma 2 (AIM2) inflammasome has been demonstrated as involved in tumor growth. In this study we used human samples of lung adenocarcinoma (LUAD) patients, taking advantage of a mouse model of smoking cessation. Human samples were stratified according to the smoking status, high-risk factor for this type of tumor. Both public transcriptomic and human samples obtained by a clinical trial proved that AIM2 was upregulated either in terms of mRNA or protein, respectively, in the tumor mass according to the TNM stage, but it did not relate to the smoking status, age and sex. The upregulation of AIM2 was correlated to an immunosuppressive environment according to resting/non-active dendritic cells (DCs) and T regulatory cells, as demonstrated in both human samples and by means of an experimental model of smoking mice. Computational analysis showed that AIM2 upregulation was correlated to both an inflammasome profile, responsible for the poor prognosis of non-smoker and smoker LUAD patients, and to a non-inflammasome profile for former smoker. In conclusion, our study demonstrated that AIM2 is involved in lung carcinogenesis either in a canonical and non-canonical manner due to an immunosuppressive microenvironment associated to a dismal prognosis of LUAD patients.
MeSH term(s)	Humans ; Mice ; Animals ; Inflammasomes/metabolism ; Adenocarcinoma of Lung/genetics ; Melanoma ; Prognosis ; Lung Neoplasms/genetics ; Tumor Microenvironment ; DNA-Binding Proteins/genetics
Chemical Substances	Inflammasomes ; AIM2 protein, human ; DNA-Binding Proteins
Language	English
Publishing date	2023-10-17
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2043785-7
ISSN	1878-1705 ; 1567-5769
ISSN (online)	1878-1705
ISSN	1567-5769
DOI	10.1016/j.intimp.2023.110990
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Article ; Online: Sex Differences in Sphingosine-1-Phosphate Levels Are Dependent on Ceramide Synthase 1 and Ceramidase in Lung Physiology and Tumor Conditions.

Terlizzi, Michela / Colarusso, Chiara / Ferraro, Giusy / Falanga, Anna / Monti, Maria Chiara / Somma, Pasquale / De Rosa, Ilaria / Panico, Luigi / Pinto, Aldo / Sorrentino, Rosalinda

International journal of molecular sciences

2023 Volume 24, Issue 13

Abstract: Sex is a biological variable that can reflect clinical outcomes in terms of quality of life, therapy effectiveness, responsiveness and/or toxicity. Sphingosine-1-phosphate (S1P) is a lipidic mediator whose activity can be influenced by sex. To evaluate ... ...

Abstract	Sex is a biological variable that can reflect clinical outcomes in terms of quality of life, therapy effectiveness, responsiveness and/or toxicity. Sphingosine-1-phosphate (S1P) is a lipidic mediator whose activity can be influenced by sex. To evaluate whether the S1P axis underlies sex 'instructions' in the lung during physiological and oncological lung conditions, sphingosine and S1P were quantified in the blood of healthy (H) volunteers, lung adenocarcinoma (ADK) and squamous cell carcinoma (SCC) patients of both sexes. S1P receptors and their metabolic enzymes were evaluated in the tissues. Circulating levels of S1P were similar among H female and male subjects and female SCC patients. Instead, male and female ADK patients had lower circulating S1P levels. S1P receptor 3 (S1PR3) was physiologically expressed in the lung, but it was overexpressed in male SCC, and female and male ADK, but not in female SCC patients, who showed a significantly reduced ceramide synthase 1 (CERS1) mRNA and an overexpression of the ceramidase (ASAH1) precursor in lung tumor tissues, compared to male SCC and both male and female ADK patients. These findings highlighted sex differences in S1P rheostat in pathological conditions, but not in physiological conditions, identifying S1P as a prognostic mediator depending on lung cancer histotype.
MeSH term(s)	Humans ; Male ; Female ; Sphingosine/metabolism ; Ceramidases/metabolism ; Sex Characteristics ; Quality of Life ; Lysophospholipids/metabolism ; Lung/metabolism ; Lung Neoplasms/metabolism
Chemical Substances	sphingosine 1-phosphate (26993-30-6) ; Sphingosine (NGZ37HRE42) ; Ceramidases (EC 3.5.1.23) ; dihydroceramide desaturase (EC 1.3.1.-) ; Lysophospholipids
Language	English
Publishing date	2023-06-29
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms241310841
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Article ; Online: Drug resistance in non-small cell lung Cancer (NSCLC): Impact of genetic and non-genetic alterations on therapeutic regimen and responsiveness.

Terlizzi, Michela / Colarusso, Chiara / Pinto, Aldo / Sorrentino, Rosalinda

Pharmacology & therapeutics

2019 Volume 202, Page(s) 140–148

Abstract: The discovery of genetic alterations, that can be targeted therapeutically, has launched a new era for lung cancer research and personalized therapy. However, not all the identified new genetic driver mutations are therapeutically targetable due to high ... ...

Abstract	The discovery of genetic alterations, that can be targeted therapeutically, has launched a new era for lung cancer research and personalized therapy. However, not all the identified new genetic driver mutations are therapeutically targetable due to high toxicity profile. On the other hand, those genetic alterations that could be pharmacologically targeted, are often subject of alternative mutations that lead to drug resistance, which represents one of the major clinical limitation. Mechanisms of acquired resistance in oncogene-driven malignancies occur after additional genetic alterations of the primary oncogene. In this scenario, the secondary genetic alteration can lead to up-regulation of bypass-signaling pathways, changes in tumor histology or alterations in drug metabolism, that are able to promote drug resistance with an ensuing lower survival rate of the patient. Another aspect to be considered is that non-genetically mutated patients still have poor pharmacological options and therefore still represent an unmet medical need. Therefore, identifying mechanisms underlying both drug resistance in genetically mutated patients and novel therapeutic alternatives for non-mutated NSCLC patients is still an area of intense investigation.
MeSH term(s)	Animals ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Carcinoma, Non-Small-Cell Lung/genetics ; Drug Resistance, Neoplasm/drug effects ; Drug Resistance, Neoplasm/genetics ; Humans ; Lung Neoplasms/drug therapy ; Lung Neoplasms/genetics ; Mutation/drug effects ; Mutation/genetics ; Signal Transduction/drug effects ; Signal Transduction/genetics ; Up-Regulation/drug effects ; Up-Regulation/genetics
Chemical Substances	Antineoplastic Agents
Language	English
Publishing date	2019-06-19
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	194735-7
ISSN	1879-016X ; 0163-7258
ISSN (online)	1879-016X
ISSN	0163-7258
DOI	10.1016/j.pharmthera.2019.06.005
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Article ; Online: Sphingosine-1-Phosphate Contributes to TLR9-Induced TNF-α Release in Lung Tumor Cells.

Terlizzi, Michela / Colarusso, Chiara / Ferraro, Giusy / Monti, Maria Chiara / Cerqua, Ida / Roviezzo, Fiorentina / Pinto, Aldo / Sorrentino, Rosalinda

Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology

2021 Volume 55, Issue 2, Page(s) 222–234

Abstract: Background/aims: Sphingosine-1-phosphate (S1P) is a membrane-derived bioactive phospholipid involved in many lung physiological and pathological processes. Higher levels of S1P have been registered in a broad range of respiratory diseases, including ... ...

Abstract	Background/aims: Sphingosine-1-phosphate (S1P) is a membrane-derived bioactive phospholipid involved in many lung physiological and pathological processes. Higher levels of S1P have been registered in a broad range of respiratory diseases, including inflammatory disorders and cancer. The aim of our study was to understand the role of S1P in healthy versus tumor cells after Toll-Like Receptors (TLRs) activation, well-known modulators of sphingolipid metabolism. Methods: Lung adenocarcinoma cells and non-pathological human fibroblasts were stimulated with unmethylated Cytosine phosphate Guanosine (CpG), the TLR9 ligand, and S1P-dependent TNF-α release was evaluated by means of ELISA. Immunofluorescence and LC-MS/MS analysis were performed to evaluate/quantify S1P generation following TLR9 activation. Results: We found that S1P was involved in TLR9-induced TNF-α release in that the inhibition of both ceramidase and sphingosine kinase I/II (SPHK I/II) significantly reduced the levels of TNF-α after TLR9 triggering in lung adenocarcinoma cells. These results were not observed in healthy fibroblasts, implying that this pathway was mainly involved in pathological conditions. Moreover, the activation of TLR4 by means of LPS did not have similar effects as in the case of CpG-stimulated TLR9. Importantly, the activation of TLR9 induced S1P generation and allowed it to interact on the outside membrane receptor S1P Conclusion: Our study identifies a novel inflammatory pathway in that TLR9 increases the pro-inflammatory cytokine release, such as TNF-α, via the induction of a ceramide/S1P imbalance in favor of S1P, adding a novel puzzle piece in TLR9-orchestrated inflammatory pathway and shedding more light on the role of the higher levels of S1P during inflammatory conditions.
MeSH term(s)	A549 Cells ; Adenocarcinoma of Lung/metabolism ; Blotting, Western ; Fluorescent Antibody Technique ; Humans ; Inflammation/immunology ; Inflammation/metabolism ; Lung/immunology ; Lung/metabolism ; Lung Neoplasms/metabolism ; Lysophospholipids/metabolism ; Sphingosine/analogs & derivatives ; Sphingosine/metabolism ; Tandem Mass Spectrometry ; Toll-Like Receptor 9/metabolism ; Tumor Necrosis Factor-alpha/metabolism
Chemical Substances	Lysophospholipids ; Toll-Like Receptor 9 ; Tumor Necrosis Factor-alpha ; sphingosine 1-phosphate (26993-30-6) ; Sphingosine (NGZ37HRE42)
Language	English
Publishing date	2021-05-04
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1067572-3
ISSN	1421-9778 ; 1015-8987
ISSN (online)	1421-9778
ISSN	1015-8987
DOI	10.33594/000000361
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Article ; Online: Intracellular Sphingosine-1-Phosphate Receptor 3 Contributes to Lung Tumor Cell Proliferation.

Terlizzi, Michela / Colarusso, Chiara / Ferraro, Giusy / Monti, Maria Chiara / Rosa, Ilaria De / Somma, Pasquale / Salvi, Rosario / Pinto, Aldo / Sorrentino, Rosalinda

Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology

2021 Volume 55, Issue 5, Page(s) 539–552

Abstract: Background/aims: The pleiotropic lipid mediator sphingosine-1-phosphate (S1P) exerts a multitude of effects on respiratory cell physiology and pathology through five S1P receptors (S1PR1-5). Epidemiological studies proved high levels of circulating S1P ... ...

Abstract	Background/aims: The pleiotropic lipid mediator sphingosine-1-phosphate (S1P) exerts a multitude of effects on respiratory cell physiology and pathology through five S1P receptors (S1PR1-5). Epidemiological studies proved high levels of circulating S1P in non-small cell lung cancer (NSCLC) patients. Studies in literature suggest that high levels of S1P support carcinogenesis but the exact mechanism is still elusive. The aim of this study was to understand the mechanism/s underlying S1P-mediated lung tumor cell proliferation. Methods: We used human samples of NSCLC, a mouse model of first-hand smoking and of Benzo(a)pyrene (BaP)-induced tumor-bearing mice and A549 lung adenocarcinoma cells. Results: We found that the expression of S1PR3 was also into the nucleus of lung cells in vitro, data that were confirmed in lung tissues of NSCLC patients, smoking and tumor bearing BaP-exposed mice. The intranuclear, but not the membrane, localization of S1PR3 was associated to S1P-mediated proliferation of lung adenocarcinoma cells. Indeed, the inhibition of the membrane S1PR3 did not alter tumor cell proliferation after Toll Like Receptor (TLR) 9 activation. Instead, according to the nuclear localization of sphingosine kinase (SPHK) II, the inhibition of the kinase completely blocked the endogenous S1P-induced tumor cell proliferation. Conclusion: These results prove that the nuclear S1PR3/SPHK II axis is involved in lung tumor cell proliferation, highlighting a novel molecular mechanism which could provide differential therapeutic approaches especially in non-responsive lung cancer patients.
MeSH term(s)	A549 Cells ; Adenocarcinoma of Lung/genetics ; Adenocarcinoma of Lung/metabolism ; Adenocarcinoma of Lung/pathology ; Animals ; Humans ; Lung Neoplasms/genetics ; Lung Neoplasms/metabolism ; Lung Neoplasms/pathology ; Mice ; Neoplasm Proteins/genetics ; Neoplasm Proteins/metabolism ; Phosphotransferases (Alcohol Group Acceptor)/metabolism ; Signal Transduction ; Sphingosine-1-Phosphate Receptors/genetics ; Sphingosine-1-Phosphate Receptors/metabolism
Chemical Substances	Neoplasm Proteins ; Sphingosine-1-Phosphate Receptors ; sphingosine-1-phosphate receptor-3, human ; Phosphotransferases (Alcohol Group Acceptor) (EC 2.7.1.-) ; sphingosine kinase (EC 2.7.1.-)
Language	English
Publishing date	2021-09-02
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1067572-3
ISSN	1421-9778 ; 1015-8987
ISSN (online)	1421-9778
ISSN	1015-8987
DOI	10.33594/000000431
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Article ; Online: Sex Differences in Sphingosine-1-Phosphate Levels Are Dependent on Ceramide Synthase 1 and Ceramidase in Lung Physiology and Tumor Conditions

Michela Terlizzi / Chiara Colarusso / Giusy Ferraro / Anna Falanga / Maria Chiara Monti / Pasquale Somma / Ilaria De Rosa / Luigi Panico / Aldo Pinto / Rosalinda Sorrentino

International Journal of Molecular Sciences, Vol 24, Iss 10841, p

2023 Volume 10841

Abstract	Sex is a biological variable that can reflect clinical outcomes in terms of quality of life, therapy effectiveness, responsiveness and/or toxicity. Sphingosine-1-phosphate (S1P) is a lipidic mediator whose activity can be influenced by sex. To evaluate whether the S1P axis underlies sex ‘instructions’ in the lung during physiological and oncological lung conditions, sphingosine and S1P were quantified in the blood of healthy (H) volunteers, lung adenocarcinoma (ADK) and squamous cell carcinoma (SCC) patients of both sexes. S1P receptors and their metabolic enzymes were evaluated in the tissues. Circulating levels of S1P were similar among H female and male subjects and female SCC patients. Instead, male and female ADK patients had lower circulating S1P levels. S1P receptor 3 (S1PR3) was physiologically expressed in the lung, but it was overexpressed in male SCC, and female and male ADK, but not in female SCC patients, who showed a significantly reduced ceramide synthase 1 (CERS1) mRNA and an overexpression of the ceramidase (ASAH1) precursor in lung tumor tissues, compared to male SCC and both male and female ADK patients. These findings highlighted sex differences in S1P rheostat in pathological conditions, but not in physiological conditions, identifying S1P as a prognostic mediator depending on lung cancer histotype.
Keywords	sphingosine-1-phosphate (S1P) ; sex differences ; S1P metabolism ; S1PR3 ; lung cancer ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610 ; 590
Language	English
Publishing date	2023-06-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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