Interferon-gamma (IFN-γ): Reviewing its mechanisms and signaling pathways on the regulation of endothelial barrier function. (June 2023)

• Record Type: Journal Article
• Authors: Ng, Chin Theng; Fong, Lai Yen; Abdullah, Muhammad Nazrul Hakim
• Is Part Of: Cytokine. Volume 166(2023)
• Publication Date: 2023-06
• Subjects: Interferon-gamma -- Endothelial cells -- Pro inflammatory cytokines; AJ Adherens junction -- cGMP Cyclic guanosine monophosphate -- CREB Cyclic adenosine monophosphate response element binding protein -- F-actin Filamentous actin -- G-actin Globular actin -- HAEC Human aortic endothelial cell -- HBMEC Human brain microvessel endothelial cell -- HUVEC Human umbilical vein endothelial cell -- IFNGR IFN-γreceptor -- IL Interleukin -- IRF Interferon regulatory factor -- ISGF3II IFN-stimulated gene factor 3 -- ISRE Interferon-stimulated response element -- JAK Janus-activated kinase -- MAPK Mitogen-activated protein kinase -- NF-κB Nuclear factor kappa B -- NO Nitric oxide -- PECAM Platelet endothelial cell adhesion molecules -- ROCK Rho-associated protein kinase -- STAT Signal transducer and activator of transcription -- TLR Toll-like receptor -- VCAM Vascular cell adhesion molecule -- VE-cadherin Vascular endothelial-cadherin; Cytokines -- Periodicals; 571.844
• DOI: 10.1016/j.cyto.2023.156208
• Languages: English
• ISSNs: 1043-4666

Abstract

Highlights: IFN-γ disrupts both endothelial and epithelial cell barrier function. IFN-γ induces phasic changes in human umbilical vein endothelial cells permeability. The signaling pathways of IFN-γ in the regulation of cell permeability might involve small GTPases, STAT1-dependent pathway, p38 MAPK and nitric oxide. Abstract: Interferon-gamma (IFN-γ) is a pleiotropic cytokine that plays a critical role in mediating an array of immune responses including promotes antiviral activity, facilitates macrophage activation, controls Th1/Th2 balance, and regulates cellular apoptosis and proliferation. A few articles have previously reviewed the effects of IFN-γ in the regulation of barrier permeability, but none of these articles focuses on barrier function of endothelial cells. This review aims to discuss the regulatory mechanisms of IFN-γ on endothelial barrier function and its underlying signaling pathways. Articles were retrieved from electronic databases such as PubMed and Google Scholar using keywords "Interferon-gamma", "endothelial cells", "barrier function", and "signaling pathway". The articles published between 2000 and 2022 that are related to the aforementioned topics were selected. A few journals published beyond this period were also included due to limited information available. The results showed that IFN-γ modulates endothelial barrier function, mainly involves small GTPases, STAT1-dependent pathway, p38 MAPK and nitric oxide. In conclusion, more in depth cellular and molecular studies are needed to elucidate the pathways of IFN-γ in the regulation of endothelial barrier function.