Direct Inhibitory Effect of the PDE4 Inhibitor Roflumilast on Neutrophil Migration in Chronic Obstructive Pulmonary Disease

Dunne, Amy E; Kawamatawong, Theerasuk; Fenwick, Peter; Davies, Ceri; Tullett, Hannah; Barnes, Peter J.; Donnelly, Louise E.

doi:10.1165/rcmb.2018-0065oc

Cited by 38 publications

(38 citation statements)

References 45 publications

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“…50 In addition, some molecules involved in the recruitment and activation of neutrophils have been shown to play an important role in the development of experimental COPD. 11,51,52 Therefore, it is conceivable that neutrophil degranulation in the lung during disease manifestation provides granule proteins as autoantigens, which enhances the corresponding autoimmune responses. One of the main functions of natural autoantibodies in healthy subjects is to neutralize target antigens, which is best exemplified by autoantibodies against cytokines.…”

Section: Discussionmentioning

confidence: 99%

“…4,7,8 On the one hand, it is widely believed that innate immunity is the leading actor in the early development of pulmonary changes in the disease and its animal models. [8][9][10][11][12] One the other hand, there is accumulating evidence that adaptive immunity plays a role in the chronic phase of COPD. For example, it has been shown that smoke cessation does not attenuate the pulmonary inflammation once COPD, 13,14 suggesting a memory adaptive immune response to non-cigarette antigens.…”

Section: Introductionmentioning

confidence: 99%

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<p>Serum Levels of Autoantibodies Against Extracellular Antigens and Neutrophil Granule Proteins Increase in Patients with COPD Compared to Non-COPD Smokers</p>

Ma¹,

Wen²,

Ju³

et al. 2020

COPD

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Background: Chronic obstructive pulmonary disease (COPD) is a highly prevalent disease leading to irreversible airflow limitation and is characterized by chronic pulmonary inflammation, obstructive bronchiolitis and emphysema. Etiologically, COPD is mediated by toxic gases and particles, eg, cigarette smoke, while the pathogenesis of the disease is largely unknown. Several lines of evidence indicate a link between COPD and autoimmunity but comprehensive studies are lacking. Methods: By using a protein microarray assaying more than 19,000 human proteins we determined in this study the autoantibody profiles of COPD and non-COPD smokers. The discovery cohort included 5 COPD patients under acute exacerbation (AECOPD) and 5 ageand gender-matched non-COPD smokers. One putative candidate autoantibody, antilactoferrin IgG, was further investigated by using immunoblotting with a large validation cohort containing 124 healthy controls, 92 patients with AECOPD and 52 patients with stable COPD. Results: We show that i) autoantigens targeted by autoantibodies with higher titers in COPD patients were enriched in extracellular regions, while those with lower titers in COPD patients were enriched in intracellular compartments. ii) levels of IgG autoantibodies against many neutrophil granule proteins were significantly higher in COPD patients than in non-COPD smokers. Furthermore, increased levels of anti-lactoferrin antibodies in COPD patients were confirmed in a cohort with a large number of samples. Conclusion: The comprehensive autoantibody profiles from COPD patients established in this study demonstrated for the first time a shift in the cellular localization of antigens targeted by autoantibodies in COPD.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

<p>Serum Levels of Autoantibodies Against Extracellular Antigens and Neutrophil Granule Proteins Increase in Patients with COPD Compared to Non-COPD Smokers</p>

Ma¹,

Wen²,

Ju³

et al. 2020

COPD

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“…In vitro, roflumilast N-oxide (RNO) suppressed neutrophil adhesion to endothelial cells [7]. Recently, Dunne et al [8] reported that roflumilast had an inhibitory effect on neutrophil migration. Neutrophils in COPD patients displayed increased chemotaxis, which was inhibited by RNO in a dose-dependent manner.…”

Section: Pde4i Mechanism Of Action In Airway Diseasesmentioning

confidence: 99%

Role of phosphodiesterase-4 inhibitors in chronic obstructive pulmonary disease

Rhee

Kim

2020

Korean J Intern Med

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Phosphodiesterase-4 inhibitors (PDE4Is) are potent anti-inf lammatory agents and roflumilast has been used to prevent acute exacerbation of chronic obstructive pulmonary disease (COPD). Roflumilast decreases neutrophil migration, restores cystic fibrosis transmembrane conductance regulator activity, and recovers glucocorticoid effects. A forced expiratory volume in 1 second of < 50%, a chronic bronchitis phenotype, high blood eosinophil levels, and a history of hospitalization are biomarkers for predicting responses to roflumilast. Adverse effects are common in clinical practice. An inhaled PDE4I has recently been developed and is under clinical trial. CHF6001 and RPL554 exhibit promise and may be future treatment options for COPD.

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“…Kemampuan suatu larutan dalam mengantarkan listrik disebut dengan konduktivitas listrik. Arus listrik dihantarkan oleh ion ion yang terkandung didalam larutan sehingga konduktivitas (178)(179)(180)(181) listrik hanya memperhitungkan banyaknya ion pada larutan.…”

Section: Konduktivitasunclassified

Studi Termodinamika Transpor Ionik Natrium Klorida Dalam Air dan Campuran Tertentu

Hidayati¹,

Zainul²

2019

Preprint

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Abstrak. Natrium klorida dikenal dengan garam dapur. Senyawa ini memiliki rumus NaCl dan larut dalam air. Natrium klorida merupakan senyawa yang berwujud padat bentuk kristal dan berwarna putih. Natrium klorida merupakan senyawa ionik karena adanya ikatan antara logam natrium dengan non logam klorin. Natrium klorida, didalam air dapat terion menjadi ion ion penyusunnya. Penulisan review ini bertujuan untuk menganalisis interaksi molekul pada NaCl yang dilarutkan dalam air. Metode yang digunakan dalam menganalisis interaksi molekul adalah dengan permodelan menggunakan aplikasi ChemDraw 3D. Sedangkan untuk parameter mobilitas ion, konduktivitas, viskositas, dan konduktivitas molar digunakan perhitungan dan data dari salah satu jurnal yang telah di review. Penggunaan ChemDraw 3D dan ChemDraw 2D sebagai langkah untuk menganalisis atom atom penyusun NaCl beserta molekul dan pergerakan molekulnya. Hasil yang didapatkan yaitu struktur natrium klorida dengan analisis molekular 2D dan 3D. Analisis jari-jari natrium klorida pada Chemdraw 3D didapatkan sebesar 2,530A, dan jari jari atom natrium dan klor masing-masingnya sebesar 1.287A dan 1.688A. Setelah dilakukan optimasi MMFF94, didapatkan energi sterik sebesar 0.00073874 kcal/mol dan energi molekul bergerak dalam 30 interaksi atomnya adalah 101,4 kcal/mol. Natrium klorida mempunyai beberapa sifat termokimia dalam fasa padat pada tekanan 1 atm dan suhu 25°C ΔGf° -411.2, kj/mol, ΔHf° -384.1S° 72.1 dan C 50.5. Mobilitas ion natrium sebesar 5,19 m 2 s -1 V -1 dan mobilitas ion klorin bernilai 7,91 m 2 s -1 V -1 .

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Direct Inhibitory Effect of the PDE4 Inhibitor Roflumilast on Neutrophil Migration in Chronic Obstructive Pulmonary Disease

Cited by 38 publications

References 45 publications

<p>Serum Levels of Autoantibodies Against Extracellular Antigens and Neutrophil Granule Proteins Increase in Patients with COPD Compared to Non-COPD Smokers</p>

<p>Serum Levels of Autoantibodies Against Extracellular Antigens and Neutrophil Granule Proteins Increase in Patients with COPD Compared to Non-COPD Smokers</p>

Role of phosphodiesterase-4 inhibitors in chronic obstructive pulmonary disease

Studi Termodinamika Transpor Ionik Natrium Klorida Dalam Air dan Campuran Tertentu

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