Dexamethasone Downregulates Expressions of 14-3-3β and γ-Isoforms in Mice with Eosinophilic Meningitis Caused by Angiostrongylus cantonensis Infection

Tsai, Hung Chin; Chen, Yu Hsin; Yen, Chuan-Min; Chung, Li Yu; Wann, Shue Ren; Lee, Susan Shin Jung; Chen, Yao Shen

doi:10.3347/kjp.2019.57.3.249

Cited by 3 publications

(4 citation statements)

References 37 publications

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“…Interestingly, 14-3-3 γ was downregulated after both IP and IT dexamethasone administration. Similarly, in mice, 14-3-3 has been shown to increase in the meninges and CSF of mice with eosinophilic meningitis after infection, and was downregulated upon dexamethasone administration . It has also been found that 14-3-3 γ upregulates glucocorticoid receptor in the liver .…”

Section: Discussionmentioning

confidence: 89%

“…Similarly, in mice, 14-3-3 has been shown to increase in the meninges and CSF of mice with eosinophilic meningitis after infection, and was downregulated upon dexamethasone administration. 48 It has also been found that 14-3-3 γ upregulates glucocorticoid receptor in the liver. 49 Our findings show that treatment with dexamethasone, a glucocorticoid, 14-3-3 levels in the perilymph are downregulated.…”

Section: Discussionmentioning

confidence: 98%

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Impact of Systemic versus Intratympanic Dexamethasone Administration on the Perilymph Proteome

et al. 2021

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Glucocorticoids are the first-line treatment for sensorineural hearing loss, but little is known about the mechanism of their protective effect or the impact of route of administration. The recent development of hollow microneedles enables safe and reliable sampling of perilymph for proteomic analysis. Using these microneedles, we investigate the effect of intratympanic (IT) versus intraperitoneal (IP) dexamethasone administration on guinea pig perilymph proteome. Guinea pigs were treated with IT dexamethasone (n = 6), IP dexamethasone (n = 8), or untreated for control (n = 8) 6 h prior to aspiration. The round window membrane (RWM) was accessed via a postauricular approach, and hollow microneedles were used to perforate the RWM and aspirate 1 μL of perilymph. Perilymph samples were analyzed by liquid chromatography–mass spectrometry-based label-free quantitative proteomics. Mass spectrometry raw data files have been deposited in an international public repository (MassIVE proteomics repository at ) under data set # MSV000086887. In the 22 samples of perilymph analyzed, 632 proteins were detected, including the inner ear protein cochlin, a perilymph marker. Of these, 14 proteins were modulated by IP, and three proteins were modulated by IT dexamethasone. In both IP and IT dexamethasone groups, VGF nerve growth factor inducible was significantly upregulated compared to control. The remaining adjusted proteins modulate neurons, inflammation, or protein synthesis. Proteome analysis facilitated by the use of hollow microneedles shows that route of dexamethasone administration impacts changes seen in perilymph proteome. Compared to IT administration, the IP route was associated with greater changes in protein expression, including proteins involved in neuroprotection, inflammatory pathway, and protein synthesis. Our findings show that microneedles can mediate safe and effective intracochlear sampling and hold promise for inner ear diagnostics.

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Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 98%

Impact of Systemic versus Intratympanic Dexamethasone Administration on the Perilymph Proteome

et al. 2021

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“…An increase in the serum concentration of 14-3-3β in the acute attack group of asthma has been found in comparison with the control group, which indicate that 14-3-3β may participate in the development of acute attack of asthma together and have some value in monitoring the state and prognosis of acute attack of asthma. However, it was that exist no statistical heterogeneity with regard to serum level of 14-3-3β between the chronic persistent group of asthma and the normal control group, which may be associated with the chronic use of ICS-LABA in chronic persistent group of asthma, because one study show that in mice with eosinophilic meningitis dexamethasone can decrease the expression of 14-3-3β protein in the CSF and in brain meninges [27].…”

Section: Discussionmentioning

confidence: 99%

Serum 14-3-3β Protein: a New Biomarker in Asthmatic Patients With Acute Attack

Wang

Rao

Cui

et al. 2021

Preprint

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Background: The determination of systemic inflammatory markers is one of the important directions to study the pathogenesis of asthma and improve the diagnosis of asthma. Current studies have found that the 14-3-3 protein family subtypes interact with target proteins to participate in the pathogenesis of a variety of immune inflammatory diseases. However, studies on serum tyrosine3-monooxygenase/tryptophan5-monooxygenase activation protein β (14-3-3β) in asthma are scarce. This study aimed to assess the clinical significance of 14-3-3β in asthmatic patients. Methods: We recruited 54 asthmatic patients with acute attack and 50 asthmatic patients with chronic persistent. The normal control group included 54 healthy individuals with similar sex-age indicators. Clinical characteristics (age, gender, height and weight), clinical indicators [fractional expiratory nitric oxide (FeNO), eosinophil count, forced vital capacity (FVC), percent of predicted FVC (FVC % predicted), forced expiratory volume in one second (FEV1), percent of predicted FEV1 (FEV1% predicted), the ratio of forced expiratory volume in one second to forced vital capacity (FEV1/FVC) and percent of predicted FEV1/FVC (FEV1/FVC% predicted)] and serum 14-3-3β levels were measured to compare among each group. Spearman’s rank correlation coefficient was used to evaluate the correlation between 14-3-3β and clinical indicators. Finally, Receiver-operating characteristic (ROC) curves analysis was used to determine the sensitivity and specificity of 14-3-3β.Results: Our results showed that median (interquartile range) of serum 14-3-3β concentration (ng/ml) in acute attack group of asthma (41.18 [33.06-51.76]) was much higher than that in normal control group (24.99 [17.43-29.91]; P<0.001) and chronic persistent group of asthma (25.88 [21.03-34.55]; P<0.001),however, it was that exist no statistical heterogeneity with regard to the serum 14-3-3β level between the chronic persistent group of asthma and the healthy individuals (P >0.05). Spearman’s correlation coefficient shows that the serum 14-3-3β level was positively correlated with FeNO (r=-0.292, P=0.032) and peripheral blood eosinophil count (r=0.328, P=0.016), and was negatively related to FEV1/FVC (r=-0.293, P=0.031) and FEV1/FVC% predicted (r=-0.299, P=0.028) in the acute attack group of asthma. At the same time, the serum 14-3-3β level was also negatively associated with FEV1 (r=-0.297, P=0.036) in the chronic persistent group of asthma. ROC curve analysis comparing acute attack group of asthma with normal control group demonstrated a significant (P<0.001) AUC of 0.90 (95% CI, 0.85–0.96). When the cut off value was 29.70 ng/ml, the ROC curve yielded a sensitivity of 92.6%, a specificity of 75.9%, a positive likelihood ratio (+LR) of 3.84, negative likelihood ratio (-LR) of 0.10 and a Youden index of 0.69 in acute attack group of asthma. ROC curve analysis comparing chronic persistent group of asthma with normal control group demonstrated no statistically significant difference (P>0.05) AUC of 0.60 (95% CI, 0.49–0.70). Conclusion: The Elevated serum 14-3-3β levels may be associated with airway inflammation and impaired bronchial patency in the acute attack of asthma. The serum 14-3-3β protein can be used to distinguish between asthmatic patients with acute attack and healthy individuals and may become a potential biomarker in asthmatic patients with acute attack.

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“…However, there was no statistical heterogeneity in the serum level of 14-3-3β between the chronic persistent group and the normal control group, which may be explained by the chronic use of ICS-LABA in the chronic persistent group. In a study of the mouse model of eosinophilic meningitis, dexamethasone was demonstrated to decrease the expression of 14-3-3β protein in the CSF and in brain meninges [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

Serum 14-3-3β protein: a new biomarker in asthmatic patients with acute exacerbation in an observational study

Wang

Rao

Cui

et al. 2021

Allergy Asthma Clin Immunol

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Background The determination of systemic inflammatory markers is one of the important directions to study the pathogenesis of asthma and improve the diagnosis of asthma. Current studies have found that the 14-3-3 protein family subtypes interact with target proteins to participate in the pathogenesis of a variety of immune inflammatory diseases. However, studies on serum tyrosine3-monooxygenase/tryptophan5-monooxygenase activation protein β (14-3-3β) in asthma are scarce. This study aimed to assess the clinical significance of 14-3-3β in asthmatic patients. Methods We recruited 54 asthmatic patients with acute exacerbation and 50 asthmatic patients with chronic persistent. The normal control group included 54 healthy individuals. Clinical characteristics, clinical indicators [fractional expiratory nitric oxide (FeNO), eosinophil count, forced vital capacity (FVC), percent of predicted FVC (FVC% predicted), forced expiratory volume in one second (FEV1), percent of predicted FEV1 (FEV1% predicted), the ratio of forced expiratory volume in one second to forced vital capacity (FEV1/FVC) and serum 14-3-3β levels were measured to compare among each group. Spearman’s rank correlation coefficient was used to evaluate the correlation between 14-3-3β and clinical indicators. Finally, Receiver-operating characteristic (ROC) curves analysis was used to determine the sensitivity and specificity of 14-3-3β. Results Our results showed that median (interquartile range) of serum 14-3-3β concentration (ng/mL) in acute exacerbation group of asthma (41.18 [33.06–51.76]) was much higher than that in normal control group (24.99 [17.43–29.91]; P < 0.001) and chronic persistent group of asthma (25.88 [21.03–34.55]; P < 0.001). Spearman’s correlation coefficient shows that the serum 14-3-3β level was positively correlated with FeNO (r = − 0.292, P = 0.032) and peripheral blood eosinophil count (r = 0.328, P = 0.016), and was negatively related to FEV1/FVC (r = − 0.293, P = 0.031) in the acute exacerbation group of asthma. At the same time, the serum 14-3-3β level was also negatively associated with FEV1 (r = − 0.297, P = 0.036) in the chronic persistent group of asthma. ROC curve analysis comparing acute exacerbation group of asthma with normal control group demonstrated a significant (P < 0.001) AUC of 0.90 (95% CI 0.85–0.96). Conclusion The serum 14-3-3β protein may become a potential biomarker in asthmatic patients with acute exacerbation.

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Dexamethasone Downregulates Expressions of 14-3-3β and γ-Isoforms in Mice with Eosinophilic Meningitis Caused by Angiostrongylus cantonensis Infection

Cited by 3 publications

References 37 publications

Impact of Systemic versus Intratympanic Dexamethasone Administration on the Perilymph Proteome

Impact of Systemic versus Intratympanic Dexamethasone Administration on the Perilymph Proteome

Serum 14-3-3β Protein: a New Biomarker in Asthmatic Patients With Acute Attack

Serum 14-3-3β protein: a new biomarker in asthmatic patients with acute exacerbation in an observational study

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