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Tiotropium Bromide Improves Neutrophilic Asthma by Recovering Histone Deacetylase 2 Activity.

التفاصيل البيبلوغرافية
العنوان: Tiotropium Bromide Improves Neutrophilic Asthma by Recovering Histone Deacetylase 2 Activity.
المؤلفون: An TJ; Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea., Kim JH; Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea., Hur J; Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea., Park CK; Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea., Lim JU; Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea., Kim S; Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea., Rhee CK; Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea., Yoon HK; Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea. cmcyhg@gmail.com.
المصدر: Journal of Korean medical science [J Korean Med Sci] 2023 Mar 27; Vol. 38 (12), pp. e91. Date of Electronic Publication: 2023 Mar 27.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Korean Academy of Medical Science Country of Publication: Korea (South) NLM ID: 8703518 Publication Model: Electronic Cited Medium: Internet ISSN: 1598-6357 (Electronic) Linking ISSN: 10118934 NLM ISO Abbreviation: J Korean Med Sci Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Seoul, Korea : Korean Academy of Medical Science, [1986-
مواضيع طبية MeSH: Asthma*/drug therapy , Histone Deacetylase 2*/metabolism , Tiotropium Bromide*/pharmacology, Animals ; Humans ; Mice ; Inflammation ; Lipopolysaccharides ; Mice, Inbred C57BL ; NF-kappa B/metabolism
مستخلص: Background: The value of tiotropium bromide (TIO) in neutrophilic asthma was meaningful in previous study. We hypothesized that TIO's mechanism of action is associated with histone deacetylase 2 (HDAC2) activity, which is key for controlling the transcription of inflammatory cytokines and usually downregulated in neutrophilic asthma.
Methods: The effects of TIO and dexamethasone (DEX) on HDAC2 activity, nuclear factor kappa B (NF-κB), and C-X-C motif chemokine ligand 1 (CXCL1) were evaluated in neutrophilic asthma mouse model (C57BL, 6-week-old). An in-vitro study was conducted using primary human bronchial/tracheal epithelial (HBE) cells from asthma patients. Western blot analyses were performed for phospho-phospholipase Cγ-1 (PLCγ-1) and inositol trisphosphate (IP 3 ) receptors (IP 3 R) with treating lipopolysaccharide (LPS) and TIO.
Results: Ovalbumin was used to induce eosinophilic inflammation in this study. After neutrophilic asthma was induced by LPS (O+L group), HDAC2 activity was diminished with increased NF-κB activity and CXCL1 compared to the control group. TIO significantly improved NF-κB activity, CXCL1, and HDAC2 activity compared with the O+L group in in-vivo study ( P < 0.05, each). Western blot analyses showed that LPS treated HBE cells from asthma patients increased PLCγ-1 and diminished IP 3 receptor levels. After TIO treatment, recovery of IP 3 R and improved PLCγ-1 levels were observed.
Conclusion: These results support the hypothesis that TIO modulates inflammation by recovering HDAC2 activity from the acetylcholine-stimulated inflammation cascade in neutrophilic asthma. The detailed inflammation cascade of recovering HDAC2 activity by TIO might be associated with PLCγ-1-IP 3 -IP 3 R mediated intracellular calcium ion pathway.
Competing Interests: The authors have no potential conflicts of interest to disclose.
(© 2023 The Korean Academy of Medical Sciences.)
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معلومات مُعتمدة: Korea Korean Academy of Tuberculosis and Respiratory Diseases
فهرسة مساهمة: Keywords: Asthma; Histone Deacetylases 2; Neutrophils; Tiotropium bromide
المشرفين على المادة: EC 3.5.1.98 (Histone Deacetylase 2)
0 (Lipopolysaccharides)
0 (NF-kappa B)
XX112XZP0J (Tiotropium Bromide)
تواريخ الأحداث: Date Created: 20230328 Date Completed: 20230405 Latest Revision: 20230405
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC10042725
DOI: 10.3346/jkms.2023.38.e91
PMID: 36974400
قاعدة البيانات: MEDLINE
الوصف
تدمد:1598-6357
DOI:10.3346/jkms.2023.38.e91