Xian'e Tang1,2, Ruhui Liu1, Youyang Zhang1, Lingfeng Zhu3, Weiqi Shi1, Yongmei Shan4, Shihao Wu5, Yuhang Li1,5, Guanghui Liu6, Wenlin Ma1,5. 1. Department of Cardiology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China. 2. School of Medicine, Hubei Minzu University, Enshi, China. 3. Department of Cardiology, Luodian Hospital, Shanghai, China. 4. Department of the Clinical Laboratory, Tongji Hospital, Tongji University, Shanghai, China. 5. Department of Geriatric Medicine, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China. 6. Department of Endocrinology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China.
Abstract
Background: Patients with myocardial infarction (MI) comorbid with the depressive disorder may have increased serum cytokine concentrations, notably, of interleukin-1 beta (IL-1β). The histone H3 lysine-27 (H3K27) demethylase Jmjd3 is crucial in cytokine regulation, and administering an H3K27 demethylase-selective inhibitor (GSK J4) might ameliorate inflammatory symptoms. We hypothesized that Jmjd3 might regulate IL-1β concentrations, thus affecting the development of post-MI depression (PMD). In this study, a mouse model was created to examine the connection between IL-1β and PMD and determine the regulatory function of cytokine in controlling inflammation and depressive symptoms. Methods: MI was induced in 30 5-week-old male C57BL/6N mice via a left coronary ligation, and MI onset was confirmed by electrocardiogram (ECG). After treatment with dimethylsulfoxide (DMSO) or GSK J4 for 14 days, the mice were subjected to tail-suspension tests (TSTs) and forced swimming tests (FSTs) before being sacrificed for tissue harvest. Results: In the TSTs, the GSK J4-treated MI mice displayed a significantly shorter immobility time than did the DMSO-treated MI mice (P<0.001). In the FSTs, the DMSO-treated MI mice showed a significantly longer immobility time than did the DMSO-treated sham-operated mice (P<0.001). The GSK J4-treated MI mice had a significantly reduced immobility time compared to the DMSO-treated MI mice (P<0.001). IL-1β expression in the myocardium, hippocampus, prefrontal cortex (PFC), and hypothalamus increased after MI onset (P=0.003, 0.015, 0.0003, and 0.013, respectively) but decreased after treatment with GSK J4 (P<0.001, P=0.005, P<0.001, P=0.018, respectively). In the myocardium and hypothalamus, Jmjd3 expression levels were lower in mice that received GSK J4 treatment than in those that received DMSO treatment (P<0.05). Conclusions: GSK J4 inhibited the cardiac expression of IL-1β and Jmjd3, and alleviated PMD in MI mice. Therefore, IL-1β and Jmjd3 may be critical in the pathogenesis of PMD, and Jmjd3 may potentially serve as a target for PMD treatment. 2022 Cardiovascular Diagnosis and Therapy. All rights reserved.
Background: Patients with myocardial infarction (MI) comorbid with the depressive disorder may have increased serum cytokine concentrations, notably, of interleukin-1 beta (IL-1β). The histone H3 lysine-27 (H3K27) demethylase Jmjd3 is crucial in cytokine regulation, and administering an H3K27 demethylase-selective inhibitor (GSK J4) might ameliorate inflammatory symptoms. We hypothesized that Jmjd3 might regulate IL-1β concentrations, thus affecting the development of post-MI depression (PMD). In this study, a mouse model was created to examine the connection between IL-1β and PMD and determine the regulatory function of cytokine in controlling inflammation and depressive symptoms. Methods: MI was induced in 30 5-week-old male C57BL/6N mice via a left coronary ligation, and MI onset was confirmed by electrocardiogram (ECG). After treatment with dimethylsulfoxide (DMSO) or GSK J4 for 14 days, the mice were subjected to tail-suspension tests (TSTs) and forced swimming tests (FSTs) before being sacrificed for tissue harvest. Results: In the TSTs, the GSK J4-treated MI mice displayed a significantly shorter immobility time than did the DMSO-treated MI mice (P<0.001). In the FSTs, the DMSO-treated MI mice showed a significantly longer immobility time than did the DMSO-treated sham-operated mice (P<0.001). The GSK J4-treated MI mice had a significantly reduced immobility time compared to the DMSO-treated MI mice (P<0.001). IL-1β expression in the myocardium, hippocampus, prefrontal cortex (PFC), and hypothalamus increased after MI onset (P=0.003, 0.015, 0.0003, and 0.013, respectively) but decreased after treatment with GSK J4 (P<0.001, P=0.005, P<0.001, P=0.018, respectively). In the myocardium and hypothalamus, Jmjd3 expression levels were lower in mice that received GSK J4 treatment than in those that received DMSO treatment (P<0.05). Conclusions: GSK J4 inhibited the cardiac expression of IL-1β and Jmjd3, and alleviated PMD in MI mice. Therefore, IL-1β and Jmjd3 may be critical in the pathogenesis of PMD, and Jmjd3 may potentially serve as a target for PMD treatment. 2022 Cardiovascular Diagnosis and Therapy. All rights reserved.
Authors: Adem Can; David T Dao; Michal Arad; Chantelle E Terrillion; Sean C Piantadosi; Todd D Gould Journal: J Vis Exp Date: 2012-01-29 Impact factor: 1.355
Authors: Adem Can; David T Dao; Chantelle E Terrillion; Sean C Piantadosi; Shambhu Bhat; Todd D Gould Journal: J Vis Exp Date: 2012-01-28 Impact factor: 1.355
Authors: Nancy Frasure-Smith; François Lespérance; Michael R Irwin; Claude Sauvé; Jacques Lespérance; Pierre Théroux Journal: Biol Psychiatry Date: 2007-01-08 Impact factor: 13.382
Authors: Jing Li; Xi Li; Qing Wang; Shuang Hu; Yongfei Wang; Frederick A Masoudi; John A Spertus; Harlan M Krumholz; Lixin Jiang Journal: Lancet Date: 2014-06-23 Impact factor: 79.321
Authors: Robert Dantzer; Jason C O'Connor; Gregory G Freund; Rodney W Johnson; Keith W Kelley Journal: Nat Rev Neurosci Date: 2008-01 Impact factor: 34.870
Authors: Piotr Przanowski; Michal Dabrowski; Aleksandra Ellert-Miklaszewska; Michal Kloss; Jakub Mieczkowski; Beata Kaza; Anna Ronowicz; Feng Hu; Arkadiusz Piotrowski; Helmut Kettenmann; Jan Komorowski; Bozena Kaminska Journal: J Mol Med (Berl) Date: 2013-10-06 Impact factor: 4.599