Targeted Modulation of Interferon Response-Related Genes with IFN-Alpha/Lambda Inhibition.

Debpali Sur, Katerina Leonova, Bar Levi, Shany Ivon Markowitz, Raichel Cohen-Harazi, Ilya Gitlin, Katerina Gurova, Andrei Gudkov, Albert Pinhasov, Igor Koman, Elimelech Nesher

International journal of molecular sciences 2022 Jun 29

filter terms:

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.

Citation

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. 2022 Jun 29;23(13)