IL (Interleukin)-10–STAT3–Galectin-3 Axis Is Essential for Osteopontin-Producing Reparative Macrophage Polarization After Myocardial Infarction

Shirakawa, Kohsuke; Endo, Jin; Kataoka, Masaharu; Katsumata, Yoshinori; Yoshida, Naohiro; Yamamoto, Tsunehisa; Isobe, Satoshi; Moriyama, Hidenori; Goto, Shinichi; Kitakata, Hiroki; Hiraide, Takahiro; Fukuda, Keiichi; Sano, Motoaki

doi:10.1161/circulationaha.118.035047

Cited by 150 publications

(125 citation statements)

References 51 publications

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“…Of the eight genes, Tlr4, Tlr9 and Tlr8 are involved in the progression of HF 7,35,36 ; silencing of the transcription factor Irf5 may be used to ameliorate HF 37 ; immune response-related genes CD80 and CD86 promise to be effective new immunotherapeutic targets in inflammation related to heart 38 ; MI could induce strong transcriptional activation of Spp1. 39 The regulation of danshen on these genes proved that danshen has reliable efficacy in treating HF. Given the significance of TLR4 in myocardial inflammation, we furtherly focused on the downstream molecular pathway of TLR4 signalling.…”

Section: Discussionmentioning

confidence: 99%

Danshen (Salvia miltiorrhiza) restricts MD2/TLR4‐MyD88 complex formation and signalling in acute myocardial infarction‐induced heart failure

Wang

Guo

et al. 2020

J Cellular Molecular Medi

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Heart failure (HF) represents a major public health burden. Inflammation has been shown to be a critical factor in the progression of HF, regardless of the aetiology. Disappointingly, the majority of clinical trials targeting aspects of inflammation in patients with HF have been largely negative. Many clinical researches demonstrate that danshen has a good efficacy on HF, and however, whether danshen exerts anti‐inflammatory effects against HF remains unclear. In our study, the employment of a water extracted and alcohol precipitated of danshen extract attenuated cardiac dysfunction and inflammation response in acute myocardial infarction‐induced HF rats. Transcriptome technique and validation results revealed that TLR4 signalling pathway was involved in the anti‐inflammation effects of danshen. In vitro, danshen reduced the release of inflammatory mediators in LPS‐stimulated RAW264.7 macrophage cells. Besides, the LPS‐stimulated macrophage conditioned media was applied to induce cardiac H9C2 cells injury, which could be attenuated by danshen. Furtherly, knock‐down and overexpression of TLR4 were utilized to confirm that danshen ameliorated inflammatory injury via MyD88‐dependent TLR4‐TRAF6‐NF‐κB signalling pathway in cardiomyocytes. Furthermore, by utilizing co‐immunoprecipitation, danshen was proved to suppress MD2/TLR4 complex formation and MyD88 recruitment. In conclusion, our results demonstrated that danshen ameliorates inflammatory injury by controlling MD2/TLR4‐MyD88 complex formation and TLR4‐TRAF6‐NF‐κB signalling pathway in acute myocardial infarction‐induced HF.

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Section: Discussionmentioning

confidence: 99%

Danshen (Salvia miltiorrhiza) restricts MD2/TLR4‐MyD88 complex formation and signalling in acute myocardial infarction‐induced heart failure

Wang

Guo

et al. 2020

J Cellular Molecular Medi

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“…Further use of Compound C inhibited AMPKa activity, and the effect of Roquin-1 on mTOR phosphorylation disappeared. Additionally, STAT3 has been shown to play an important role in the polarization and function of mø (35). Decreased flagellin induced TNF-a and IL-6 expression and cell proliferation in mø with LY294002 and wortmannin.…”

Section: Discussionmentioning

confidence: 99%

Roquin-1 Regulates Macrophage Immune Response and Participates in Hepatic Ischemia–Reperfusion Injury

Zheng

Wei

Zhang

et al. 2020

The Journal of Immunology

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With the development of liver surgery, ischemia-reperfusion (IR) injury has received increasing attention. Roquin-1 has been shown to play an important role in innate immune and immune balance. We demonstrate that Roquin-1 expression increased at 1 h after IR and then decreased in C57B/L mice. The immunofluorescence double-label showed that Roquin-1 was mainly expressed in macrophages (mø). Furthermore, we used clodronate liposomes to remove mø, and injected the bone marrowderived mø (BMDM) through the tail vein in 1 h before IR. We found that liver IR injury was aggravated by Roquin-1 interference. The results of PCR and ELISA suggested that after interference with Roquin-1, mø increased toward M1 and decreased toward M2. Then, interference with Roquin-1 promoted the polarization of mø to M1 and inhibited the polarization of M2. By Western blot technology and AMPKa and mTOR inhibitors, we found that Roquin-1 promotes the phosphorylation of mTOR and STAT3 by inhibiting the phosphorylation of AMPKa. We used AICAR to activate AMPKa in mø and found that the level of ubiquitination of AMPKa was decreased after activation of AMPKa. Furthermore, by bioinformatics methods, we identified potential ubiquitination sites on AMPKa. By the point mutation experiments in vitro, we confirmed that the ubiquitination of these sites is regulated by Roquin-1. Meanwhile, Roquin-1 interference inhibited the activation and function of AMPKa. This topic describes the protection of liver IR injury by Roquin-1 and discusses its main mechanism for regulating AMPKa activity through ubiquitination and affecting the polarization of mø.

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“…Galectin-3 promotes fibroblast proliferation and transformation and stimulates the phagocytosis of apoptotic cells and cellular debris by macrophages. Galectin-3 is highly expressed and secreted by macrophages [44,45]. Interleukin (IL)-10 increases the expression of intracellular galectin-3 through activation of signal transducer and activator of transcription 3 (STAT3) [44].…”

Section: Discussionmentioning

confidence: 99%

“…Galectin-3 is highly expressed and secreted by macrophages [44,45]. Interleukin (IL)-10 increases the expression of intracellular galectin-3 through activation of signal transducer and activator of transcription 3 (STAT3) [44]. The low levels of galectin-3 and IL-10 during the physiologically stressful Antarctica trek is another indicator of diminished immune function.…”

Section: Discussionmentioning

confidence: 99%

Proteomics-Based Detection of Immune Dysfunction in an Elite Adventure Athlete Trekking Across the Antarctica

Nieman

Groen²,

Pugachev³

et al. 2020

Proteomes

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Proteomics monitoring of an elite adventure athlete (age 33 years) was conducted over a 28-week period that culminated in the successful, solo, unassisted, and unsupported two month trek across the Antarctica (1500 km). Training distress was monitored weekly using a 19-item, validated training distress scale (TDS). Weekly dried blood spot (DBS) specimens were collected via fingerprick blood drops onto standard blood spot cards. DBS proteins were measured with nano-electrospray ionization liquid chromatography tandem mass spectrometry (nanoLC-MS/MS) in data-independent acquisition (DIA) mode, and 712 proteins were identified and quantified. The 28-week period was divided into time segments based on TDS scores, and a contrast analysis between weeks five and eight (low TDS) and between weeks 20 and 23 (high TDS, last month of Antarctica trek) showed that 31 proteins (n = 20 immune related) were upregulated and 35 (n = 17 immune related) were downregulated. Protein–protein interaction (PPI) networks supported a dichotomous immune response. Gene ontology (GO) biological process terms for the upregulated immune proteins showed an increase in regulation of the immune system process, especially inflammation, complement activation, and leukocyte mediated immunity. At the same time, GO terms for the downregulated immune-related proteins indicated a decrease in several aspects of the overall immune system process including neutrophil degranulation and the antimicrobial humoral response. These proteomics data support a dysfunctional immune response in an elite adventure athlete during a sustained period of mental and physical distress while trekking solo across the Antarctica.

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IL (Interleukin)-10–STAT3–Galectin-3 Axis Is Essential for Osteopontin-Producing Reparative Macrophage Polarization After Myocardial Infarction

Cited by 150 publications

References 51 publications

Danshen (Salvia miltiorrhiza) restricts MD2/TLR4‐MyD88 complex formation and signalling in acute myocardial infarction‐induced heart failure

Danshen (Salvia miltiorrhiza) restricts MD2/TLR4‐MyD88 complex formation and signalling in acute myocardial infarction‐induced heart failure

Roquin-1 Regulates Macrophage Immune Response and Participates in Hepatic Ischemia–Reperfusion Injury

Proteomics-Based Detection of Immune Dysfunction in an Elite Adventure Athlete Trekking Across the Antarctica

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