Isoflurane attenuates LPS-induced acute lung injury by targeting miR-155-HIF1-alpha

Hu, Rong; Zhang, Ying; Yang, Xiaohua; Jia, Yan; Sun, Yinghao; Chen, Zhifeng; Jiang, Hong

doi:10.2741/4302

Cited by 20 publications

(4 citation statements)

References 44 publications

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“…A known molecule targeted by HIF-1α in other systems is miR-155, which is pro-inflammatory in many lineages (41). Studies show that miR-155 possesses a hypoxia response element in its promoter region, further connecting HIF-1α and miR-155 (42).…”

Section: Discussionmentioning

confidence: 99%

Lactic Acid Suppresses IL-33–Mediated Mast Cell Inflammatory Responses via Hypoxia-Inducible Factor-1α–Dependent miR-155 Suppression

Abebayehu

Spence

Qayum

et al. 2016

The Journal of Immunology

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Lactic acid (LA) is present in tumors, asthma, and wound healing, environments with elevated IL-33 and mast cell infiltration. While IL-33 is a potent mast cell activator, how LA affects IL-33-mediated mast cell function is unknown. To investigate this, mouse bone marrow-derived mast cells (BMMC) were cultured with or without LA and activated with IL-33. LA reduced IL-33-mediated cytokine and chemokine production. Using inhibitors for monocarboxylate transporters (MCT) or replacing LA with sodium lactate revealed that LA effects are MCT-1- and pH-dependent. LA selectively altered IL-33 signaling, suppressing TAK1, JNK, ERK, and NFκB phosphorylation, but not p38 phosphorylation. LA effects in other contexts have been linked to HIF-1α, which was enhanced in BMMC treated with LA. Since HIF-1α has been shown to regulate the microRNA miR-155 in other systems, LA effects on miR-155-5p and -3p species were measured. In fact, LA selectively suppressed miR-155-5p in a HIF-1α-dependent manner. Moreover, overexpressing miR-155-5p, but not miR-155-3p, abolished LA effects on IL-33-induced cytokine production. These in vitro effects of reducing cytokines were consistent in vivo, since LA injected intraperitoneally into C57BL/6 mice suppressed IL-33-induced plasma cytokine levels. Lastly, IL-33 effects on primary human mast cells were suppressed by LA in an MCT-dependent manner. Our data demonstrate that LA, present in inflammatory and malignant microenvironments, can alter mast cell behavior to suppress inflammation.

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Section: Discussionmentioning

confidence: 99%

Lactic Acid Suppresses IL-33–Mediated Mast Cell Inflammatory Responses via Hypoxia-Inducible Factor-1α–Dependent miR-155 Suppression

Abebayehu

Spence

Qayum

et al. 2016

The Journal of Immunology

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“…16,17,18,19,20,21,22,23,24,36 miR-155 is a critical miRNA that regulates inflammation, and can be highly induced by LPS treatment in vitro and in vivo . 41,42,43 However, the role of miR-155 in LPS-induced myocardial dysfunction is still unclear. To the best of our knowledge, this study firstly demonstrates a notable increase in miR-155 expression level in hearts challenged with LPS.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of miR-155 Protects Against LPS-induced Cardiac Dysfunction and Apoptosis in Mice

Wang

Bei

Huang

et al. 2016

Molecular Therapy - Nucleic Acids

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Sepsis-induced myocardial dysfunction represents a major cause of death in intensive care units. Dysregulated microRNAs (miR)-155 has been implicated in multiple cardiovascular diseases and miR-155 can be induced by lipopolysaccharide (LPS). However, the role of miR-155 in LPS-induced cardiac dysfunction is unclear. Septic cardiac dysfunction in mice was induced by intraperitoneal injection of LPS (5 mg/kg) and miR-155 was found to be significantly increased in heart challenged with LPS. Pharmacological inhibition of miR-155 using antagomiR improved cardiac function and suppressed cardiac apoptosis induced by LPS in mice as determined by echocardiography, terminal deoxynucleotidyl transferase nick-end labeling (TUNEL) assay, and Western blot for Bax and Bcl-2, while overexpression of miR-155 using agomiR had inverse effects. Pea15a was identified as a target gene of miR-155, mediating its effects in controlling apoptosis of cardiomyocytes as evidenced by luciferase reporter assays, quantitative real time-polymerase chain reaction, Western blot, and TUNEL staining. Noteworthy, miR-155 was also found to be upregulated in the plasma of patients with septic cardiac dysfunction compared to sepsis patients without cardiac dysfunction, indicating a potential clinical relevance of miR-155. The receiver-operator characteristic curve indicated that plasma miR-155 might be a biomarker for sepsis patients developing cardiac dysfunction. Therefore, inhibition of miR-155 represents a novel therapy for septic myocardial dysfunction.

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“…IL-33 is produced by tissue resident endothelial, epithelial and fibroblast cells upon damage, while LPS is often present at wound site due to bacterial contamination. 33–35 Therefore, we examined how fibronectin-coated scaffolds with varying morphologies altered IL-33- and LPS-mediated mast cell cytokine production.…”

Section: Resultsmentioning

confidence: 99%

Polymer scaffold architecture is a key determinant in mast cell inflammatory and angiogenic responses

Abebayehu

Spence

McClure

et al. 2019

J Biomedical Materials Res

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Implanted polymer scaffolds can induce inflammation leading to the foreign body response (FBR), fibrosis, and implant failure. Thus, it is important to understand how immune cells interact with scaffolds to mitigate inflammation and promote a regenerative response. We previously demonstrated that macrophage phenotype is modulated by fiber and pore diameters of an electrospun scaffold. However, it is unclear if this effect is consistent among other innate immune cells. Mast cells are inflammatory sentinels that play a vital role in the FBR of implanted biomaterials, as well as angiogenesis. We determined if altering electrospun scaffold architecture modulates mast cell responses, with the goal of promoting regenerative cell-scaffold interactions. Polydioxanone (PDO) scaffolds were made from 60 mg/mL or 140 mg/mL PDO solutions, yielding structures with divergent fiber and pore diameters. Mouse mast cells plated on these scaffolds were activated with IL-33 or lipo-polysaccharide (LPS). Relative to the 60 mg/mL scaffold, 140 mg/mL scaffolds yielded less IL-6 and TNF, and greater VEGF secretion. Pores >4–6 μm elicited less IL-6 and TNF secretion. IL-33-induced VEGF regulation was more complex, showing effects of both pore size and fiber diameter. These data indicate parameters that can predict mast cell responses to scaffolds, informing biomaterial design to increase wound healing and diminish implant rejection.

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Isoflurane attenuates LPS-induced acute lung injury by targeting miR-155-HIF1-alpha

Cited by 20 publications

References 44 publications

Lactic Acid Suppresses IL-33–Mediated Mast Cell Inflammatory Responses via Hypoxia-Inducible Factor-1α–Dependent miR-155 Suppression

Lactic Acid Suppresses IL-33–Mediated Mast Cell Inflammatory Responses via Hypoxia-Inducible Factor-1α–Dependent miR-155 Suppression

Inhibition of miR-155 Protects Against LPS-induced Cardiac Dysfunction and Apoptosis in Mice

Polymer scaffold architecture is a key determinant in mast cell inflammatory and angiogenic responses

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