Inhibition of interleukin-6 signaling attenuates aortitis, left ventricular hypertrophy and arthritis in interleukin-1 receptor antagonist deficient mice

Hada, Yoshiko; Uchida, Haruhito A.; Mukai, Tomoyuki; Kojima, Fumio; Yoshida, Masashi; Takeuchi, Hidemi; Kakio, Yuki; Otaka, Nozomu; Morita, Yoshitaka; Wada, Jun

doi:10.1042/cs20201036

Cited by 8 publications

(7 citation statements)

References 69 publications

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“…However, we found a significantly higher number of IL-1β- and IL-6-positive cells in the IL1rn −/− group within the abdominal aortic wall. This study, therefore, corroborates the preferential involvement of these two cytokines in the pathophysiology of this model, as previously observed in this mouse model and in GCA based on fundamental and targeted cytokine therapeutic data [ 15 , 28 – 32 ]. Second, considering second-generation mice, the TBR measured on PET-MR was significantly higher in the descending thoracic aorta of five 9-week-old IL1rn −/− mice born and housed in an SPF environment than in the wild-type group, suggesting a role of the microbiota, probably that in the gut [ 33 ], in the induction of inflammatory aortitis in this model.…”

Section: Discussionsupporting

confidence: 90%

[18F]FDG PET-MR characterization of aortitis in the IL1rn−/− mouse model of giant-cell arteritis

Deshayes,

Baugé,

Dupont

et al. 2023

EJNMMI Res

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Background Metabolic imaging is routinely used to demonstrate aortitis in patients with giant-cell arteritis. We aimed to investigate the preclinical model of aortitis in BALB/c IL1rn−/− mice using [18F]fluorodeoxyglucose ([18F]FDG) positron emission tomography–magnetic resonance (PET-MR), gamma counting and immunostaining. We used 15 first-generation specific and opportunistic pathogen-free (SOPF) 9-week-old IL1rn−/− mice, 15 wild-type BALB/cAnN mice and 5 s-generation specific pathogen-free (SPF) 9-week-old IL1rn−/−. Aortic [18F]FDG uptake was assessed as the target-to-background ratio (TBR) using time-of-flight MR angiography as vascular landmarks. Results [18F]FDG uptake measured by PET or gamma counting was similar in the first-generation SOPF IL1rn−/− mice and the wild-type group (p > 0.05). However, the first-generation IL1rn−/− mice exhibited more interleukin-1β (p = 0.021)- and interleukin-6 (p = 0.019)-positive cells within the abdominal aorta than the wild-type mice. In addition, the second-generation SPF group exhibited significantly higher TBR (p = 0.0068) than the wild-type mice on the descending thoracic aorta, unlike the first-generation SOPF IL1rn−/− mice. Conclusions In addition to the involvement of interleukin-1β and -6 in IL1rn−/− mouse aortitis, this study seems to validate [18F]FDG PET-MR as a useful tool for noninvasive monitoring of aortitis in this preclinical model.

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Section: Discussionsupporting

confidence: 90%

[18F]FDG PET-MR characterization of aortitis in the IL1rn−/− mouse model of giant-cell arteritis

Deshayes,

Baugé,

Dupont

et al. 2023

EJNMMI Res

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“…In the transcriptome sequencing experiment, we found that IL-13Rα2, Tnfaip3, Tnfrsf14, and Tnfrsf9 were upregulated in TNF-α-stimulated RAW264.7 cells, which was related with the development of inflammation (Wilson et al, 2011). The expression of Il1rn was upregulated in WBT + TNFα-stimulated RAW264.7 cells, suggesting WBT could ameliorate inflammatory conditions stimulated by TNF-α (Matsuki et al, 2005;Hada et al, 2020). These findings were consistent with ELISA results about IL-1β and IL-6.…”

Section: Discussionsupporting

confidence: 83%

Identification of the Main Active Components and Mechanism of Wang Bi Tablet in Treating Rheumatoid Arthritis Based on Integrative Pharmacology

Jiao

Chen

et al. 2021

Front. Pharmacol.

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Wang Bi tablet (WBT) is used to treat rheumatoid arthritis (RA) in China. We employed integrative pharmacology, including rapid analysis of chemical composition, pharmacological experiment, and network pharmacology analysis, to elucidate the active components and mechanism underlying the effect of WBT against RA. The chemical fingerprint of WBT was revealed by UPLC-QTOF-MS/MS, and the chemical composition was identified. The anti-inflammatory effect of WBT was evaluated in TNF-α-stimulated RAW264.7 cells by ELISA and transcriptome sequencing. Network pharmacology analysis, functional enrichment analysis, and network visualization were performed. A total of 293 chemical constituents were preliminarily identified or tentatively characterized in WBT extract, and they effectively inhibited inflammatory response in TNF-α-stimulated RAW264.7 cells. Forty-eight key active constituents were identified based on high-frequency binding to hub targets and their corresponding targets number. Next, 135 corresponding hub genes, which may be the putative targets of WBT in treating RA, were selected. Functionally, the putative targets were significantly associated with the inflammatory immune response regulation module, energy metabolism regulation module, and cell function regulation module, corresponding to the traditional efficacy of WBT. In summary, this study revealed, for the first time using integrative pharmacology, that WBT may attenuate RA through the inflammation-immune regulation system.

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“…Left ventricular diastolic dysfunction, in fact, has been associated to the release of pro-inflammatory cytokines, prolonged hypoxemia, and excessive activation of neuroendocrine and autonomic nerve function, further aggravating the hormonal storms that foster myocardial hypertrophy and fibrosis ( 32 ). Experimental evidence has shown that blockade of interleukin 6, a typical inflammatory cytokine, attenuates left ventricular hypertrophy ( 33 ).…”

Section: Discussionmentioning

confidence: 99%

Case report: Diagnosis of apical hypertrophic cardiomyopathy that escaped clinical and echocardiographic investigations for twenty years: Reasons and clinical implications

Caiati

Stanca

Lepera

2023

Front. Cardiovasc. Med.

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BackgroundApical hypertrophic cardiomyopathy (ApHCM) is a rare form of hypertrophic cardiomyopathy which predominantly affects the apex of the left ventricle. The diagnosis can be challenging due to several factors, ranging from no typical clinical and electrocardiogram (EKG) findings to potential difficulties in executing and interpreting the echocardiographic examination.Case presentationWe report the case of an 84-year-old woman who came to our echo-lab to undergo a routine echocardiogram. She had a history of permanent atrial fibrillation, paced rhythm and previous episodes of heart failure (HF), allegedly explained by a diagnosis of hypertensive heart disease that had been confirmed many times over the previous 20 years. The clinical examination and the EKG were unremarkable. The echocardiographic images were poor quality. But a senior cardiologist, expert in imaging and echocardiography, noted the lack of delineation of the endocardial border of the left ventricular (LV) apex region. Contrast echocardiography was performed and severe apical hypertrophy discovered.ConclusionApHCM can be a challenging diagnosis. Contrast echocardiography must always be applied in cases of poor delineation of the LV apical endocardial border at baseline echocardiography. Timely detection and appropriate lifestyle intervention might slow the development of LV hypertrophy, and possibly minimize and delay heart failure (HF) related symptoms and arrhythmias. The prognosis remains relatively benign during long term follow-up.

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Inhibition of interleukin-6 signaling attenuates aortitis, left ventricular hypertrophy and arthritis in interleukin-1 receptor antagonist deficient mice

Cited by 8 publications

References 69 publications

[18F]FDG PET-MR characterization of aortitis in the IL1rn−/− mouse model of giant-cell arteritis

[18F]FDG PET-MR characterization of aortitis in the IL1rn−/− mouse model of giant-cell arteritis

Identification of the Main Active Components and Mechanism of Wang Bi Tablet in Treating Rheumatoid Arthritis Based on Integrative Pharmacology

Case report: Diagnosis of apical hypertrophic cardiomyopathy that escaped clinical and echocardiographic investigations for twenty years: Reasons and clinical implications

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