دورية أكاديمية
أعرض في EDS

Activator protein transcription factors coordinate human IL-33 expression from noncanonical promoters in chronic airway disease.

التفاصيل البيبلوغرافية
العنوان: Activator protein transcription factors coordinate human IL-33 expression from noncanonical promoters in chronic airway disease.
المؤلفون: Raphael HE; Department of Medicine, Division of Pulmonary and Critical Care Medicine., Hassan GF; Department of Medicine, Division of Pulmonary and Critical Care Medicine., Osorio OA; Department of Medicine, Division of Pulmonary and Critical Care Medicine., Cohen LS; Department of Medicine, Division of Pulmonary and Critical Care Medicine., Payne MD; Department of Medicine, Division of Pulmonary and Critical Care Medicine., Katz-Kiriakos E; Department of Medicine, Division of Pulmonary and Critical Care Medicine., Tata I; Department of Medicine, Division of Pulmonary and Critical Care Medicine., Hicks J; Department of Medicine, Division of Pulmonary and Critical Care Medicine., Byers DE; Department of Medicine, Division of Pulmonary and Critical Care Medicine., Zhang B; Department of Developmental Biology, and., Alexander-Brett J; Department of Medicine, Division of Pulmonary and Critical Care Medicine.; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
المصدر: JCI insight [JCI Insight] 2024 Mar 08; Vol. 9 (5). Date of Electronic Publication: 2024 Mar 08.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: American Society for Clinical Investigation Country of Publication: United States NLM ID: 101676073 Publication Model: Electronic Cited Medium: Internet ISSN: 2379-3708 (Electronic) Linking ISSN: 23793708 NLM ISO Abbreviation: JCI Insight Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Ann Arbor, Michigan : American Society for Clinical Investigation, [2016]-
مواضيع طبية MeSH: Interleukin-33*/genetics , Pulmonary Disease, Chronic Obstructive*/genetics, Humans ; Proto-Oncogene Proteins c-fos/genetics ; Proto-Oncogene Proteins c-jun/metabolism ; Transcription Factor AP-1/genetics ; Transcription Factor AP-1/metabolism
مستخلص: IL-33 is a cytokine central to type 2 immune pathology in chronic airway disease. This cytokine is abundantly expressed in the respiratory epithelium and increased in disease, but how expression is regulated is undefined. Here we show that increased IL33 expression occurs from multiple noncanonical promoters in human chronic obstructive pulmonary disease (COPD), and it facilitates production of alternatively spliced isoforms in airway cells. We found that phorbol 12-myristate 13-acetate (PMA) can activate IL33 promoters through protein kinase C in primary airway cells and lines. Transcription factor (TF) binding arrays combined with RNA interference identified activator protein (AP) TFs as regulators of baseline and induced IL33 promoter activity. ATAC-Seq and ChIP-PCR identified chromatin accessibility and differential TF binding as additional control points for transcription from noncanonical promoters. In support of a role for these TFs in COPD pathogenesis, we found that AP-2 (TFAP2A, TFAP2C) and AP-1 (FOS and JUN) family members are upregulated in human COPD specimens. This study implicates integrative and pioneer TFs in regulating IL33 promoters and alternative splicing in human airway basal cells. Our work reveals a potentially novel approach for targeting IL-33 in development of therapeutics for COPD.
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معلومات مُعتمدة: K08 HL121168 United States HL NHLBI NIH HHS; P30 DK065988 United States DK NIDDK NIH HHS; R01 HL152245 United States HL NHLBI NIH HHS; R35 GM142917 United States GM NIGMS NIH HHS
فهرسة مساهمة: Keywords: COPD; Cytokines; Immunology; Pulmonology; Transcription
المشرفين على المادة: 0 (Interleukin-33)
0 (Proto-Oncogene Proteins c-fos)
0 (Proto-Oncogene Proteins c-jun)
0 (Transcription Factor AP-1)
0 (IL33 protein, human)
SCR Disease Name: Pulmonary Disease, Chronic Obstructive, Severe Early-Onset
تواريخ الأحداث: Date Created: 20240308 Date Completed: 20240311 Latest Revision: 20240330
رمز التحديث: 20240330
مُعرف محوري في PubMed: PMC10972587
DOI: 10.1172/jci.insight.174786
PMID: 38456508
قاعدة البيانات: MEDLINE
الوصف
تدمد:2379-3708
DOI:10.1172/jci.insight.174786