Deficiency of IKKɛ inhibits inflammation and induces cardiac protection in high-fat diet-induced obesity in mice

Cao, Changchun; Li, Liangpeng; Chen, Wen; Zhu, Yifan; Qi, Yongchao; Wang, Xiaodi; Wan, Xin; Chen, Xin

doi:10.3892/ijmm.2014.1746

Cited by 15 publications

(15 citation statements)

References 28 publications

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“…The membranes were blocked in Tris-buffered saline with Tween 20 (TBST) containing 5% skimmed milk powder for 1 h at room temperature and incubated with various primary antibodies overnight at 4°C. Following incubation with secondary antibodies for 1 h at room temperature, membranes were washed with TBST four times, as previously described (11). Specific proteins were detected using an enhanced chemiluminescence reagent (GE Healthcare, Piscataway, NJ, USA) and captured on Hyperfilm (GE Healthcare).…”

Section: Methodsmentioning

confidence: 99%

Toll-like receptor-4 pathway is required for the pathogenesis of human chronic endometritis

Xie

et al. 2014

Experimental and Therapeutic Medicine

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Toll-like receptor (TLR) signal transduction is a central component of the primary innate immune response to pathogenic challenge. TLR4, a member of the TLR family, is highly expressed in the endometrial cells of the uterus and could thus be a key link between human chronic endometritis (CE) and the immune system. However, the exact biological function of TLR4 in human CE remains largely unexplored. The present study aimed to examine the role of TLR4 in human CE. A comprehensive expression and activation analysis of TLR4 in the endometrial cells of the uterus from patients with human CE (n=25) and normal endometrial (NE) tissue (n=15) was performed. Western blot analyses demonstrated that compared with NE, the protein expression TLR4 markedly increased in human CE. Endometrial tissue scrapings were also used for total RNA extraction and were transcribed and amplified by reverse transcription quantitative polymerase chain reaction. The results showed that significant upregulation of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), and downregulation of IL-10 mRNA was observed in CE compared with the NE group. Furthermore, the protein of the signaling adapter myeloid differentiation factor-88 and the accessory molecules (TNF receptor associated factor 6 and transforming growth factor-β-activated kinase 1) were also detected in all the assayed tissues. Of note, differential expression (CE versus NE) was observed by immunoblotting at each level of the nuclear factor-κB signaling cascade, including inhibitor κBα and P65 (all P<0.05). The altered TLR4 and its corresponding downstream signaling molecules in CE cells may be of relevance for the progression of the human CE. These findings indicate that the evaluation of expression patterns of TLR4 holds promise for the treatment of human CE.

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Section: Methodsmentioning

confidence: 99%

Toll-like receptor-4 pathway is required for the pathogenesis of human chronic endometritis

Xie

et al. 2014

Experimental and Therapeutic Medicine

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“…Human and Apoe −/− Mice. Previous studies have shown that IKKε plays an important role in regulating cardiovascular disease [6,7]. Therefore, we assessed IKKε expression in abdominal aortic tissues taken from AAA patients and nonaneurysmal controls.…”

Section: Expression Of Ikkε Is Upregulated In Aaa Tissues Frommentioning

confidence: 99%

“…Induced AAA Formation in Apoe-Deficient Mice. Because IKKε activity has been linked to the pathology of inflammatory diseases [5,7], a recent study identified an antiinflammatory drug, amlexanox, as a selective inhibitor of IKKε and an approved small-molecule therapeutic presently used in the clinic to treat aphthous ulcers and in clinical trials for obesity [20]. We assumed that amlexanox administration could efficiently inhibit Ang II-induced AAA in mice; pharmacological inhibition studies were employed using to address this hypothesis.…”

Section: Pharmacological Inhibition Of Ikkε Mitigates Ang Ii-mentioning

confidence: 99%

“…Inhibitor of kappa B kinase epsilon (IKKε) is an important member of the IKK family, and its overexpression leads to malignant transformation of human disease [4,5]. Using mouse deficiency in IKKε and apolipoprotein E (Apoe), we recently showed that IKKε is a key player in the pathogenesis of the cardiovascular disease [6,7]; deficiency of IKKε has been suggested to have an anti-inflammatory effect and to inhibit malignant transformation [8,9]. Expression of IKKε was upregulated in AAA patients when compared to a normal group.…”

Section: Introductionmentioning

confidence: 99%

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IKK Epsilon Deficiency Attenuates Angiotensin II-Induced Abdominal Aortic Aneurysm Formation in Mice by Inhibiting Inflammation, Oxidative Stress, and Apoptosis

Chai

Tao

et al. 2020

Oxidative Medicine and Cellular Longevity

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Abdominal aortic aneurysm (AAA) is a vascular disorder that is considered a chronic inflammatory disease. However, the precise molecular mechanisms involved in AAA have not been fully elucidated. Recently, significant progress has been made in understanding the function and mechanism of action of inhibitor of kappa B kinase epsilon (IKKε) in inflammatory and metabolic diseases. The angiotensin II- (Ang II-) induced or pharmacological inhibitors were established to test the effects of IKKε on AAA in vivo. After mice were continuously stimulated with Ang II for 28 days, morphologically, we found that knockout of IKKε reduced AAA formation and drastically reduced maximal diameter and severity. We also observed a decrease in elastin degradation and medial destruction, which were independent of systolic blood pressure or plasma cholesterol concentrations. Western blot analyses and immunohistochemical staining were carried out to measure IKKε expression in AAA tissues and cell lines. AAA phenotype of mice was measured by ultrasound and biochemical indexes. In zymography, immunohistology staining, immunofluorescence staining, and reactive oxygen species (ROS) analysis, TUNEL assay was used to examine the effects of IKKε on AAA progression in AAA mice. IKKε deficiency significantly inhibited inflammatory macrophage infiltration, matrix metalloproteinase (MMP) activity, ROS production, and vascular smooth muscle cell (VSMC) apoptosis. We used primary mouse aortic VSMC isolated from apolipoprotein E (Apoe) −/− and Apoe−/−IKKε−/− mice. Mechanistically, IKKε deficiency blunted the activation of the ERK1/2 pathway. The IKKε inhibitor, amlexanox, has the same impact in AAA. Our results demonstrate a critical role of IKKε in AAA formation induced by Ang II in Apoe−/− mice. Targeting IKKε may constitute a novel therapeutic strategy to prevent AAA progression.

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“…DAPI was used to counterstain the nuclei. Samples were then covered with mounting media (Invitrogen; Thermo Fisher Scientific, Inc.), overlaid with coverslips and examined under a fluorescence microscope (Axio Scope A1; Carl Zeiss AG, Oberkochen, Germany) following the method described in previous studies (19,20). …”

Section: Methodsmentioning

confidence: 99%

Expression of pericardial fluid T-cells and related inflammatory cytokines in patients with chronic heart failure

Iskandar

Liu

Fei

et al. 2017

Experimental and Therapeutic Medicine

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Pericardial fluid, as a biochemical indicator of heart status, directly indicates pathological alteration to the heart. The accumulation of pericardial fluid can be attributed to an underlying systemic or local inflammatory process. However, the pericardial fluid expression of cellular surface markers, as well as several cytokines in chronic heart failure (CHF), remain unclear. In order to evaluate these issues further the pericardial fluid expression of several cytokines and the surface expression of activity markers between CHF patients and non-heart failure (NHF) patients were analyzed. The pericardial fluid expression of cytokines was measured by immunofluorescence and biomarker of plasma N-terminal propeptide of B-type natriuretic peptide (NT-proBNP), while pericardial fluid levels of soluble glycoprotein 130 (sgp130) were analyzed by ELISA in 50 CHF and 24 NHF patients. In addition, the surface expression of activation markers for T-cells was measured by immunohistochemistry. Patients with CHF demonstrated increased levels of plasma NT-proBNP and pericardial fluid sgp130. Surface expression of cellular activation markers CD25 and Foxp3 in the pericardial fluid was increased in patients with CHF. Moreover, the pro- and anti-inflammatory cytokines interferon (IFN)-γ, interleukin (IL)-6 and IL-10 in patients with CHF also demonstrated an increased expression within its pericardial fluid. In addition, there was infiltration of inflammatory cells and enhanced expression of inflammatory cytokines in the pericardial fluid of patients with CHF, which may reflect T cell activation, suggesting that systemic inflammation is important in the progression of CHF. This evidence could indicate a possible novel target for future therapeutics and prevention of CHF.

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Deficiency of IKKɛ inhibits inflammation and induces cardiac protection in high-fat diet-induced obesity in mice

Cited by 15 publications

References 28 publications

Toll-like receptor-4 pathway is required for the pathogenesis of human chronic endometritis

Toll-like receptor-4 pathway is required for the pathogenesis of human chronic endometritis

IKK Epsilon Deficiency Attenuates Angiotensin II-Induced Abdominal Aortic Aneurysm Formation in Mice by Inhibiting Inflammation, Oxidative Stress, and Apoptosis

Expression of pericardial fluid T-cells and related inflammatory cytokines in patients with chronic heart failure

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