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Publication : Interleukin-6 knockout reverses macrophage differentiation imbalance and alleviates cardiac dysfunction in aging mice.

First Author  Wang Y Year  2020
Journal  Aging (Albany NY) Volume  12
Issue  20 Pages  20184-20197
PubMed ID  33099539 Mgi Jnum  J:309266
Mgi Id  MGI:6705470 Doi  10.18632/aging.103749
Citation  Wang Y, et al. (2020) Interleukin-6 knockout reverses macrophage differentiation imbalance and alleviates cardiac dysfunction in aging mice. Aging (Albany NY) 12(20):20184-20197
abstractText  Several interleukins (ILs) have been shown to be involved in aging, but the effects of IL-6 on aging-related cardiac dysfunction remain unknown. In this study, the expression and sources of cardiac IL-6 in aging hearts were investigated for the first time. The results showed that cardiac IL-6 expression in mice gradually increased with age, and the expression at 16 months, 20 months and 25 months was higher than that at 3 months. In addition, cardiac macrophages (Mos) were shown to be the main sources of IL-6 in aging mice. IL-6 knockout (KO) significantly alleviated cardiac dysfunction, increased M2 macrophage (Mo2) differentiation, reduced M1 macrophage (Mo1) differentiation and protected against cardiomyocyte apoptosis in aging mice. IL-6 KO also reversed the stimulatory effect of doxorubicin (DOX) treatment on Mo1s and the inhibitory effect of DOX treatment on Mo2s in vitro. Furthermore, the mRNA expression of both aging markers and apoptosis-related markers was markedly inhibited by IL-6 KO. Our results suggest that aging can be significantly reversed by IL-6 KO and that the mechanisms of this effect are related to alleviation of Mo1/Mo2 imbalance and protection against apoptosis in cardiomyocytes.
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