Ghadir Amin, Rana Ghali, Nada J Habeichi, Ziad Mallat, George W Booz, Fouad A Zouein
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引用次数: 0
Abstract
Kidney damage is a serious prevalent complication that occurs after a myocardial infarction (MI) and is associated with worse outcomes. Interleukin-33 (IL-33), a member of the IL-1 superfamily, functions as an alarmin that is released upon necrosis or tissue damage to alert immune cells expressing the ST2L receptor. IL-33 is increased in kidney disease, and recent studies have shown that the IL-33/ST2 axis is instrumental in both disease progression and repair. In this study, we investigated the effect of IL-33 administration on kidneys in C57BL6/J male mice 4 and 7 days after the induction of MI. The mice received either IL-33 or vehicle (PBS) treatment. Cardiac systolic function and systemic inflammation were assessed, and kidneys were subjected to histological and molecular analysis. The administration of IL-33 for 4 days post-MI improved renal structure consistent with reduced expression of profibrotic markers, reduced apoptosis, and increased expression of the anti-inflammatory cytokine IL-4. In addition, IL-33 administration enhanced the levels of Sirtuin3, nicotinamide phosphoribosyltransferase, and the renal nicotinamide adenine dinucleotide pool which are critical for mitochondrial function and energy production, indicating metabolic benefits. However, this protection seems to be lost with the continued administration of IL-33 for 7 days post-MI coinciding with aggravated cardiac dysfunction and increased systemic inflammation. These findings demonstrate that while IL-33 treatment can help improve kidney damage post-MI in the short term, extended treatment may not be beneficial. This may be due to the direct effects of IL-33 on the kidneys or indirectly mediated by adverse cardiac remodeling influencing the cardiorenal crosstalk.
期刊介绍:
Journal of Interferon & Cytokine Research (JICR) provides the latest groundbreaking research on all aspects of IFNs and cytokines. The Journal delivers current findings on emerging topics in this niche community, including the role of IFNs in the therapy of diseases such as multiple sclerosis, the understanding of the third class of IFNs, and the identification and function of IFN-inducible genes.