Induction of Inflammation Disrupts the Negative Interplay between STING and S1P Axis That Is Observed during Physiological Conditions in the Lung
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 be...
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MDPI AG
2023-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/9/8303 |
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| author | Michela Terlizzi Chiara Colarusso Anna Falanga Pasquale Somma Ilaria De Rosa Luigi Panico Aldo Pinto Piera Maiolino Rosalinda Sorrentino |
| author_facet | Michela Terlizzi Chiara Colarusso Anna Falanga Pasquale Somma Ilaria De Rosa Luigi Panico Aldo Pinto Piera Maiolino Rosalinda Sorrentino |
| author_sort | Michela Terlizzi |
| collection | DOAJ |
| description | 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. |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T04:16:18Z |
| publishDate | 2023-05-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-8e70cf2926fa404f98a772381b26a8072023-11-17T23:07:43ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-05-01249830310.3390/ijms24098303Induction of Inflammation Disrupts the Negative Interplay between STING and S1P Axis That Is Observed during Physiological Conditions in the LungMichela Terlizzi0Chiara Colarusso1Anna Falanga2Pasquale Somma3Ilaria De Rosa4Luigi Panico5Aldo Pinto6Piera Maiolino7Rosalinda Sorrentino8Department of Pharmacy (DIFARMA), University of Salerno, 84084 Salerno, ItalyDepartment of Pharmacy (DIFARMA), University of Salerno, 84084 Salerno, ItalyDepartment of Pharmacy (DIFARMA), University of Salerno, 84084 Salerno, ItalyAnatomy and Pathology Unit, Ospedale dei Colli, AORN, “Monaldi”, 84131 Naples, ItalyAnatomy and Pathology Unit, Ospedale dei Colli, AORN, “Monaldi”, 84131 Naples, ItalyAnatomy and Pathology Unit, Ospedale dei Colli, AORN, “Monaldi”, 84131 Naples, ItalyDepartment of Pharmacy (DIFARMA), University of Salerno, 84084 Salerno, Italy“Fondazione Pascale”, National Institute of Tumor, 80131 Naples, ItalyDepartment of Pharmacy (DIFARMA), University of Salerno, 84084 Salerno, ItalyThe 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.https://www.mdpi.com/1422-0067/24/9/8303STINGsphingosine-1-phosphate (S1P)IL-6inflammationlung cancer |
| spellingShingle | Michela Terlizzi Chiara Colarusso Anna Falanga Pasquale Somma Ilaria De Rosa Luigi Panico Aldo Pinto Piera Maiolino Rosalinda Sorrentino Induction of Inflammation Disrupts the Negative Interplay between STING and S1P Axis That Is Observed during Physiological Conditions in the Lung International Journal of Molecular Sciences STING sphingosine-1-phosphate (S1P) IL-6 inflammation lung cancer |
| title | Induction of Inflammation Disrupts the Negative Interplay between STING and S1P Axis That Is Observed during Physiological Conditions in the Lung |
| title_full | Induction of Inflammation Disrupts the Negative Interplay between STING and S1P Axis That Is Observed during Physiological Conditions in the Lung |
| title_fullStr | Induction of Inflammation Disrupts the Negative Interplay between STING and S1P Axis That Is Observed during Physiological Conditions in the Lung |
| title_full_unstemmed | Induction of Inflammation Disrupts the Negative Interplay between STING and S1P Axis That Is Observed during Physiological Conditions in the Lung |
| title_short | Induction of Inflammation Disrupts the Negative Interplay between STING and S1P Axis That Is Observed during Physiological Conditions in the Lung |
| title_sort | induction of inflammation disrupts the negative interplay between sting and s1p axis that is observed during physiological conditions in the lung |
| topic | STING sphingosine-1-phosphate (S1P) IL-6 inflammation lung cancer |
| url | https://www.mdpi.com/1422-0067/24/9/8303 |
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