The multiple roles of interferon regulatory factor family in health and disease

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Oct. 9, 2024

Interferon Regulatory Factors (IRFs), a family of transcription factors, profoundly influence the immune system, impacting both physiological and pathological processes. This review explores diverse functions nine mammalian IRF members, each featuring conserved domains essential for interactions with other factors cofactors. These allow IRFs to modulate broad spectrum processes, encompassing host defense, response, cell development. Conversely, their pivotal role in regulation implicates them pathophysiology various diseases, such as infectious autoimmune disorders, metabolic cancers. In this context, display dichotomous nature, functioning tumor suppressors promoters, contingent upon specific disease milieu. Post-translational modifications IRFs, including phosphorylation ubiquitination, play crucial modulating function, stability, activation. As prospective biomarkers therapeutic targets, present promising opportunities intervention. Further research is needed elucidate precise mechanisms governing regulation, potentially pioneering innovative strategies, particularly cancer treatment, where equilibrium activities paramount importance.

Language: Английский

Adenosine A2A Receptor Activation Alleviated Disease of Mice with Systemic Candida albicans Infection by Regulating Macrophage Function

Journal of Inflammation Research, Journal Year: 2025, Volume and Issue: Volume 18, P. 3283 - 3294

Published: March 1, 2025

Purpose: The incidence of candidemia, mediated by systemic Candida albicans ( C. ) infection, was increasing. It is an urgent need to understand the underlying disease mechanisms identify new therapeutic targets. This study aimed investigate roles adenosine–adenosine receptor signal in infection. Methods: candidemia mice models (named CA mice) were established tail intravenous injection . Mice treated with NECA (a metabolically stable adenosine analogue) or agonists targeting different receptors (A1R, A2AR, A2BR and A3R). survival rate, renal fungal load tissue damage investigated. Bone marrow-derived macrophages (BMDM) isolated cultured effects agonist on phagocytosis, killing function polarization macrophages. Results: In mice, we observed that A2AR treatment significantly alleviated sepsis score increased rate. Moreover, injury reduced treatment. However, other (ie, A1R, A3R) activation have no effect mice. could reduce macrophage infiltration kidney production inflammatory cytokine IL-6 adenosine-A2AR signaling enhance antifungal capacity promoted toward M2 subtype. Conclusion: Activation axis polarization, enhanced host defense against candidiasis. be considered as a potential strategy candidemia. Keywords: , receptor, injury,

Language: Английский

ALDH2 regulates mesenchymal stem cell senescence via modulation of mitochondrial homeostasis

Free Radical Biology and Medicine, Journal Year: 2024, Volume and Issue: 223, P. 172 - 183

Published: Aug. 4, 2024

Although mitochondrial aldehyde dehydrogenase 2 (ALDH2) is involved in aging and aging-related diseases, its role the regulation of human mesenchymal stem cell (MSC) senescence has not been investigated. This study aimed to determine ALDH2 regulating MSC illustrate potential mechanisms. MSCs were isolated from young (YMSCs) aged donors (AMSCs). Senescence-associated β-galactosidase (SA-β-gal) staining Western blotting used assess senescence. Reactive oxygen species (ROS) generation membrane determined evaluate function. We showed that expression increased alongside cellular MSCs. Overexpression accelerated YMSC whereas down-regulation alleviated premature senescent phenotypes AMSCs. Transcriptome biochemical analyses revealed an elevated ROS level dysfunction contributed function Using molecular docking, we identified interferon regulatory factor 7 (IRF7) as target ALDH2. Mechanistically, ectopic led by increasing stability IRF7 through a direct physical interaction. These effects partially reversed knockdown IRF7. findings highlight crucial driving homeostasis, providing novel strategy against diseases.

Language: Английский