Targeted Modulation of Interferon Response-Related Genes with IFN-Alpha/Lambda Inhibition
Interferon (IFN) signaling resulting from external or internal inflammatory processes initiates the rapid release of cytokines and chemokines to target viral or bacterial invasion, as well as cancer and other diseases. Prolonged exposure to IFNs, or the overexpression of other cytokines, leads to im...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/13/7248 |
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| author | Debpali Sur Katerina Leonova Bar Levi Shany Ivon Markowitz Raichel Cohen-Harazi Ilya Gitlin Katerina Gurova Andrei Gudkov Albert Pinhasov Igor Koman Elimelech Nesher |
| author_facet | Debpali Sur Katerina Leonova Bar Levi Shany Ivon Markowitz Raichel Cohen-Harazi Ilya Gitlin Katerina Gurova Andrei Gudkov Albert Pinhasov Igor Koman Elimelech Nesher |
| author_sort | Debpali Sur |
| collection | DOAJ |
| description | Interferon (IFN) signaling resulting from external or internal inflammatory processes initiates the rapid release of cytokines and chemokines to target viral or bacterial invasion, as well as cancer and other diseases. Prolonged exposure to IFNs, or the overexpression of other cytokines, leads to immune exhaustion, enhancing inflammation and leading to the persistence of infection and promotion of disease. Hence, to control and stabilize an excessive immune response, approaches for the management of inflammation are required. The potential use of peptides as anti-inflammatory agents has been previously demonstrated. Our team discovered, and previously published, a 9-amino-acid cyclic peptide named ALOS4 which exhibits anti-cancer properties in vivo and in vitro. We suggested that the anti-cancer effect of ALOS4 arises from interaction with the immune system, possibly through the modulation of inflammatory processes. Here, we show that treatment with ALOS4 decreases basal cytokine levels in mice with chronic inflammation and prolongs the lifespan of mice with acute systemic inflammation induced by irradiation. We also show that pretreatment with ALOS4 reduces the expression of IFN alpha, IFN lambda, and selected interferon-response genes triggered by polyinosinic-polycytidylic acid (Poly I:C), a synthetic analog of viral double-stranded RNA, while upregulating the expression of other genes with antiviral activity. Hence, we conclude that ALOS4 does not prevent IFN signaling, but rather supports the antiviral response by upregulating the expression of interferon-response genes in an interferon-independent manner. |
| first_indexed | 2024-03-09T21:48:42Z |
| format | Article |
| id | doaj.art-2f9f73aed8074b5abc734e63b59ca20d |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T21:48:42Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-2f9f73aed8074b5abc734e63b59ca20d2023-11-23T20:10:36ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-06-012313724810.3390/ijms23137248Targeted Modulation of Interferon Response-Related Genes with IFN-Alpha/Lambda InhibitionDebpali Sur0Katerina Leonova1Bar Levi2Shany Ivon Markowitz3Raichel Cohen-Harazi4Ilya Gitlin5Katerina Gurova6Andrei Gudkov7Albert Pinhasov8Igor Koman9Elimelech Nesher10Department of Molecular Biology, Faculty of Natural Sciences, Ariel University, Ariel 4070000, IsraelDepartment of Cell Stress Biology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USADepartment of Molecular Biology, Faculty of Natural Sciences, Ariel University, Ariel 4070000, IsraelInstitute for Personalized and Translational Medicine, Ariel University, Ariel 4070000, IsraelInstitute for Personalized and Translational Medicine, Ariel University, Ariel 4070000, IsraelDepartment of Cell Stress Biology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USADepartment of Cell Stress Biology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USADepartment of Cell Stress Biology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USADepartment of Molecular Biology, Faculty of Natural Sciences, Ariel University, Ariel 4070000, IsraelInstitute for Personalized and Translational Medicine, Ariel University, Ariel 4070000, IsraelDepartment of Molecular Biology, Faculty of Natural Sciences, Ariel University, Ariel 4070000, IsraelInterferon (IFN) signaling resulting from external or internal inflammatory processes initiates the rapid release of cytokines and chemokines to target viral or bacterial invasion, as well as cancer and other diseases. Prolonged exposure to IFNs, or the overexpression of other cytokines, leads to immune exhaustion, enhancing inflammation and leading to the persistence of infection and promotion of disease. Hence, to control and stabilize an excessive immune response, approaches for the management of inflammation are required. The potential use of peptides as anti-inflammatory agents has been previously demonstrated. Our team discovered, and previously published, a 9-amino-acid cyclic peptide named ALOS4 which exhibits anti-cancer properties in vivo and in vitro. We suggested that the anti-cancer effect of ALOS4 arises from interaction with the immune system, possibly through the modulation of inflammatory processes. Here, we show that treatment with ALOS4 decreases basal cytokine levels in mice with chronic inflammation and prolongs the lifespan of mice with acute systemic inflammation induced by irradiation. We also show that pretreatment with ALOS4 reduces the expression of IFN alpha, IFN lambda, and selected interferon-response genes triggered by polyinosinic-polycytidylic acid (Poly I:C), a synthetic analog of viral double-stranded RNA, while upregulating the expression of other genes with antiviral activity. Hence, we conclude that ALOS4 does not prevent IFN signaling, but rather supports the antiviral response by upregulating the expression of interferon-response genes in an interferon-independent manner.https://www.mdpi.com/1422-0067/23/13/7248IFN-αIFN-λpeptideALOS4inflammationcytokines |
| spellingShingle | Debpali Sur Katerina Leonova Bar Levi Shany Ivon Markowitz Raichel Cohen-Harazi Ilya Gitlin Katerina Gurova Andrei Gudkov Albert Pinhasov Igor Koman Elimelech Nesher Targeted Modulation of Interferon Response-Related Genes with IFN-Alpha/Lambda Inhibition International Journal of Molecular Sciences IFN-α IFN-λ peptide ALOS4 inflammation cytokines |
| title | Targeted Modulation of Interferon Response-Related Genes with IFN-Alpha/Lambda Inhibition |
| title_full | Targeted Modulation of Interferon Response-Related Genes with IFN-Alpha/Lambda Inhibition |
| title_fullStr | Targeted Modulation of Interferon Response-Related Genes with IFN-Alpha/Lambda Inhibition |
| title_full_unstemmed | Targeted Modulation of Interferon Response-Related Genes with IFN-Alpha/Lambda Inhibition |
| title_short | Targeted Modulation of Interferon Response-Related Genes with IFN-Alpha/Lambda Inhibition |
| title_sort | targeted modulation of interferon response related genes with ifn alpha lambda inhibition |
| topic | IFN-α IFN-λ peptide ALOS4 inflammation cytokines |
| url | https://www.mdpi.com/1422-0067/23/13/7248 |
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