دورية أكاديمية
Lysine-specific demethylase 1 (LSD1) serves as an potential epigenetic determinant to regulate inflammatory responses in mastitis.
| العنوان: | Lysine-specific demethylase 1 (LSD1) serves as an potential epigenetic determinant to regulate inflammatory responses in mastitis. |
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| المؤلفون: | Jingjing W; College of Veterinary Medicine, Jilin University, Jilin, Changchun 130062, People's Republic of China; College of Life Science and Engineering, Foshan University, Foshan, Guangdong 528231, People's Republic of China., Zhikai W; College of Life Science and Engineering, Foshan University, Foshan, Guangdong 528231, People's Republic of China., Xingyi Z; College of Life Science and Engineering, Foshan University, Foshan, Guangdong 528231, People's Republic of China., Peixuan L; College of Life Science and Engineering, Foshan University, Foshan, Guangdong 528231, People's Republic of China., Yiwu F; College of Life Science and Engineering, Foshan University, Foshan, Guangdong 528231, People's Republic of China., Xia W; College of Life Science and Engineering, Foshan University, Foshan, Guangdong 528231, People's Republic of China., Youpeng S; College of Life Science and Engineering, Foshan University, Foshan, Guangdong 528231, People's Republic of China., Ershun Z; College of Life Science and Engineering, Foshan University, Foshan, Guangdong 528231, People's Republic of China., Zhengtao Y; College of Veterinary Medicine, Jilin University, Jilin, Changchun 130062, People's Republic of China; College of Life Science and Engineering, Foshan University, Foshan, Guangdong 528231, People's Republic of China. Electronic address: yangzhengtao01@sina.com. |
| المصدر: | International immunopharmacology [Int Immunopharmacol] 2021 Feb; Vol. 91, pp. 107324. Date of Electronic Publication: 2020 Dec 29. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Science Country of Publication: Netherlands NLM ID: 100965259 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1878-1705 (Electronic) Linking ISSN: 15675769 NLM ISO Abbreviation: Int Immunopharmacol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Amsterdam ; New York : Elsevier Science, c2001- |
| مواضيع طبية MeSH: | Epigenesis, Genetic*/drug effects, Epithelial Cells/*enzymology , Histone Demethylases/*metabolism , Mammary Glands, Human/*enzymology , Mastitis/*enzymology, Animals ; Anti-Inflammatory Agents/pharmacology ; Cells, Cultured ; Cytokines/genetics ; Cytokines/metabolism ; Disease Models, Animal ; Enzyme Inhibitors/pharmacology ; Epithelial Cells/drug effects ; Epithelial Cells/pathology ; Female ; Histone Demethylases/antagonists & inhibitors ; Histone Demethylases/genetics ; Humans ; Inflammation Mediators/metabolism ; Lipopolysaccharides ; Mammary Glands, Human/drug effects ; Mammary Glands, Human/pathology ; Mastitis/chemically induced ; Mastitis/genetics ; Mastitis/prevention & control ; Mice, Inbred BALB C ; NF-kappa B/metabolism ; Mice |
| مستخلص: | It is well-established that lysine-specific demethylase 1 (LSD1) is the first identified histone demethylase. Based on its demethylase enzymatic activity, LSD1 plays a pivotal role in vast range of cellular processes and cancers, but the understanding of its effects on inflammation is relatively limited. Using in vivo models of lipopolysaccharide (LPS)-induced inflammation and in vitro assays in mouse mammary epithelial cells, we identified the novel regulatory roles and underlying mechanisms of LSD1 on LPS-induced mastitis. Mammary gland and cells were collected for the following experiments after treatment. Histological changes were determined by H&E. Western blot analysis was used to detect the protein expression. ELISA and real-time PCR were used to evaluate protein and mRNA expression of inflammatory genes. Our results showed that LPS treatment resulted in a significant increase in LSD1 protein expression. GSK-LSD1 is a selective inhibitor of LSD1 enzyme activity. Treatment of mice with GSK-LSD1 inhibited LSD1 activity, reduced inflammatory cells recruitment to tissues and attenuated LPS-induced damage in mammary gland. Mechanistic investigations suggested that LSD1 inhibition led to the increase of histone H3K4me2 and H3K9me2. Furthermore, GSK-LSD1 inhibition of LSD1 further inhibited nuclear factor κ-B (NF-κB) signaling cascades, and subsequently inhibited the production of cytokines (TNF-α, IL-6 and IL-1β) in mammary gland. Taken together, our data reveal LSD1 as a potential regulator of inflammation and improve our understanding of epigenetic control on inflammation. (Copyright © 2020 Elsevier B.V. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Inflammation; Lipopolysaccharide; Lysine-specific demethylase 1; Mastitis; NF-κB |
| المشرفين على المادة: | 0 (Anti-Inflammatory Agents) 0 (Cytokines) 0 (Enzyme Inhibitors) 0 (Inflammation Mediators) 0 (Lipopolysaccharides) 0 (NF-kappa B) 0 (lipopolysaccharide, E coli O55-B5) EC 1.14.11.- (Histone Demethylases) EC 1.14.11.- (KDM1a protein, mouse) |
| تواريخ الأحداث: | Date Created: 20210101 Date Completed: 20210526 Latest Revision: 20240226 |
| رمز التحديث: | 20240226 |
| DOI: | 10.1016/j.intimp.2020.107324 |
| PMID: | 33385711 |
| قاعدة البيانات: | MEDLINE |
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