Impaired translation of CCAAT/enhancer binding protein α mRNA in bronchial smooth muscle cells of asthmatic patients
Bronchial smooth muscle (BSM) cells of asthmatic patients have an impaired expression of CCAAT/enhancer binding protein (C/EBP) α, which is associated with increased proliferation. We sought to assess the translational regulation of CEBPA mRNA in cultured BSM cells of healthy control subjects (n = 1...
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Published in | Journal of allergy and clinical immunology Vol. 123; no. 3; pp. 639 - 645 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Mosby, Inc
01.03.2009
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Subjects | |
Online Access | Get full text |
ISSN | 0091-6749 1097-6825 1097-6825 |
DOI | 10.1016/j.jaci.2008.11.006 |
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Abstract | Bronchial smooth muscle (BSM) cells of asthmatic patients have an impaired expression of CCAAT/enhancer binding protein (C/EBP) α, which is associated with increased proliferation.
We sought to assess the translational regulation of
CEBPA mRNA in cultured BSM cells of healthy control subjects (n = 11) and asthmatic patients (n = 12).
Translation efficiency was studied by using a translation control reporter system driven by the control elements present in the
CEBPA mRNA. Translation efficiency was determined by the ratio of 2 artificial hemagglutinin (HA.11) proteins: p23 and p12. We also analyzed levels of proteins that control translation of
CEBPA mRNA, namely heterogeneous nuclear ribonucleoprotein E2, calreticulin, eukaryotic translation initiation factor (eIF4E), and 4E binding protein.
Compared with healthy control subjects, BSM cells of asthmatic patients proliferate faster (2.1-fold) and are primed for IL-6 secretion. Real-time RT-PCR showed that BSM cells of asthmatic patients express normal levels of
CEBPA mRNA, whereas they express lower levels of C/EBPα (p42). Transient transfections with the translation control reporter system construct showed a disturbed p12/p23 ratio in BSM cells of asthmatic patients relative to healthy control subjects, which coincided with lower levels of eIF4E.
BSM cells of asthmatic patients have normal levels of
CEBPA mRNA but inadequately reinitiate the translation into C/EBPα. Impaired translation control upstream of eIF4E might underlie the observed increased proliferation and priming of BSM cells of asthmatic patients. |
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AbstractList | Bronchial smooth muscle (BSM) cells of asthmatic patients have an impaired expression of CCAAT/enhancer binding protein (C/EBP) alpha, which is associated with increased proliferation.BACKGROUNDBronchial smooth muscle (BSM) cells of asthmatic patients have an impaired expression of CCAAT/enhancer binding protein (C/EBP) alpha, which is associated with increased proliferation.We sought to assess the translational regulation of CEBPA mRNA in cultured BSM cells of healthy control subjects (n = 11) and asthmatic patients (n = 12).OBJECTIVEWe sought to assess the translational regulation of CEBPA mRNA in cultured BSM cells of healthy control subjects (n = 11) and asthmatic patients (n = 12).Translation efficiency was studied by using a translation control reporter system driven by the control elements present in the CEBPA mRNA. Translation efficiency was determined by the ratio of 2 artificial hemagglutinin (HA.11) proteins: p23 and p12. We also analyzed levels of proteins that control translation of CEBPA mRNA, namely heterogeneous nuclear ribonucleoprotein E2, calreticulin, eukaryotic translation initiation factor (eIF4E), and 4E binding protein.METHODSTranslation efficiency was studied by using a translation control reporter system driven by the control elements present in the CEBPA mRNA. Translation efficiency was determined by the ratio of 2 artificial hemagglutinin (HA.11) proteins: p23 and p12. We also analyzed levels of proteins that control translation of CEBPA mRNA, namely heterogeneous nuclear ribonucleoprotein E2, calreticulin, eukaryotic translation initiation factor (eIF4E), and 4E binding protein.Compared with healthy control subjects, BSM cells of asthmatic patients proliferate faster (2.1-fold) and are primed for IL-6 secretion. Real-time RT-PCR showed that BSM cells of asthmatic patients express normal levels of CEBPA mRNA, whereas they express lower levels of C/EBPalpha (p42). Transient transfections with the translation control reporter system construct showed a disturbed p12/p23 ratio in BSM cells of asthmatic patients relative to healthy control subjects, which coincided with lower levels of eIF4E.RESULTSCompared with healthy control subjects, BSM cells of asthmatic patients proliferate faster (2.1-fold) and are primed for IL-6 secretion. Real-time RT-PCR showed that BSM cells of asthmatic patients express normal levels of CEBPA mRNA, whereas they express lower levels of C/EBPalpha (p42). Transient transfections with the translation control reporter system construct showed a disturbed p12/p23 ratio in BSM cells of asthmatic patients relative to healthy control subjects, which coincided with lower levels of eIF4E.BSM cells of asthmatic patients have normal levels of CEBPA mRNA but inadequately reinitiate the translation into C/EBPalpha. Impaired translation control upstream of eIF4E might underlie the observed increased proliferation and priming of BSM cells of asthmatic patients.CONCLUSIONBSM cells of asthmatic patients have normal levels of CEBPA mRNA but inadequately reinitiate the translation into C/EBPalpha. Impaired translation control upstream of eIF4E might underlie the observed increased proliferation and priming of BSM cells of asthmatic patients. Bronchial smooth muscle (BSM) cells of asthmatic patients have an impaired expression of CCAAT/enhancer binding protein (C/EBP) α, which is associated with increased proliferation. We sought to assess the translational regulation of CEBPA mRNA in cultured BSM cells of healthy control subjects (n = 11) and asthmatic patients (n = 12). Translation efficiency was studied by using a translation control reporter system driven by the control elements present in the CEBPA mRNA. Translation efficiency was determined by the ratio of 2 artificial hemagglutinin (HA.11) proteins: p23 and p12. We also analyzed levels of proteins that control translation of CEBPA mRNA, namely heterogeneous nuclear ribonucleoprotein E2, calreticulin, eukaryotic translation initiation factor (eIF4E), and 4E binding protein. Compared with healthy control subjects, BSM cells of asthmatic patients proliferate faster (2.1-fold) and are primed for IL-6 secretion. Real-time RT-PCR showed that BSM cells of asthmatic patients express normal levels of CEBPA mRNA, whereas they express lower levels of C/EBPα (p42). Transient transfections with the translation control reporter system construct showed a disturbed p12/p23 ratio in BSM cells of asthmatic patients relative to healthy control subjects, which coincided with lower levels of eIF4E. BSM cells of asthmatic patients have normal levels of CEBPA mRNA but inadequately reinitiate the translation into C/EBPα. Impaired translation control upstream of eIF4E might underlie the observed increased proliferation and priming of BSM cells of asthmatic patients. Bronchial smooth muscle (BSM) cells of asthmatic patients have an impaired expression of CCAAT/enhancer binding protein (C/EBP) alpha, which is associated with increased proliferation. We sought to assess the translational regulation of CEBPA mRNA in cultured BSM cells of healthy control subjects (n = 11) and asthmatic patients (n = 12). Translation efficiency was studied by using a translation control reporter system driven by the control elements present in the CEBPA mRNA. Translation efficiency was determined by the ratio of 2 artificial hemagglutinin (HA.11) proteins: p23 and p12. We also analyzed levels of proteins that control translation of CEBPA mRNA, namely heterogeneous nuclear ribonucleoprotein E2, calreticulin, eukaryotic translation initiation factor (eIF4E), and 4E binding protein. Compared with healthy control subjects, BSM cells of asthmatic patients proliferate faster (2.1-fold) and are primed for IL-6 secretion. Real-time RT-PCR showed that BSM cells of asthmatic patients express normal levels of CEBPA mRNA, whereas they express lower levels of C/EBPalpha (p42). Transient transfections with the translation control reporter system construct showed a disturbed p12/p23 ratio in BSM cells of asthmatic patients relative to healthy control subjects, which coincided with lower levels of eIF4E. BSM cells of asthmatic patients have normal levels of CEBPA mRNA but inadequately reinitiate the translation into C/EBPalpha. Impaired translation control upstream of eIF4E might underlie the observed increased proliferation and priming of BSM cells of asthmatic patients. Background Bronchial smooth muscle (BSM) cells of asthmatic patients have an impaired expression of CCAAT/enhancer binding protein (C/EBP) α, which is associated with increased proliferation. Objective We sought to assess the translational regulation of CEBPA mRNA in cultured BSM cells of healthy control subjects (n = 11) and asthmatic patients (n = 12). Methods Translation efficiency was studied by using a translation control reporter system driven by the control elements present in the CEBPA mRNA. Translation efficiency was determined by the ratio of 2 artificial hemagglutinin (HA.11) proteins: p23 and p12. We also analyzed levels of proteins that control translation of CEBPA mRNA, namely heterogeneous nuclear ribonucleoprotein E2, calreticulin, eukaryotic translation initiation factor (eIF4E), and 4E binding protein. Results Compared with healthy control subjects, BSM cells of asthmatic patients proliferate faster (2.1-fold) and are primed for IL-6 secretion. Real-time RT-PCR showed that BSM cells of asthmatic patients express normal levels of CEBPA mRNA, whereas they express lower levels of C/EBPα (p42). Transient transfections with the translation control reporter system construct showed a disturbed p12/p23 ratio in BSM cells of asthmatic patients relative to healthy control subjects, which coincided with lower levels of eIF4E. Conclusion BSM cells of asthmatic patients have normal levels of CEBPA mRNA but inadequately reinitiate the translation into C/EBPα. Impaired translation control upstream of eIF4E might underlie the observed increased proliferation and priming of BSM cells of asthmatic patients. |
Author | Baraket, Melissa Miglino, Nicola Tamm, Michael Roth, Michael Borger, Peter Black, Judith L. |
Author_xml | – sequence: 1 givenname: Peter surname: Borger fullname: Borger, Peter email: pieter.borger@unibas.ch organization: Pulmonary Cell Research, Department of Biomedicine, University Hospital Basel, Basel, Switzerland – sequence: 2 givenname: Nicola surname: Miglino fullname: Miglino, Nicola organization: Pulmonary Cell Research, Department of Biomedicine, University Hospital Basel, Basel, Switzerland – sequence: 3 givenname: Melissa surname: Baraket fullname: Baraket, Melissa organization: Pharmacology, University of Sydney, Sydney, Australia – sequence: 4 givenname: Judith L. surname: Black fullname: Black, Judith L. organization: Pharmacology, University of Sydney, Sydney, Australia – sequence: 5 givenname: Michael surname: Tamm fullname: Tamm, Michael organization: Pulmonary Cell Research, Department of Biomedicine, University Hospital Basel, Basel, Switzerland – sequence: 6 givenname: Michael surname: Roth fullname: Roth, Michael organization: Pulmonary Cell Research, Department of Biomedicine, University Hospital Basel, Basel, Switzerland |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/19121862$$D View this record in MEDLINE/PubMed |
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Keywords | C/EBPα C/EBP eIF4E LP 4EBP bronchial smooth muscle cell hyperplasia Asthma messenger RNA translation PDGF TCRS mTOR uORF HA BSM SP hnRNPE2 Platelet-derived growth factor Heterogeneous nuclear ribonucleoprotein E2 Hemagglutinin Translation control reporter system Long peptide Bronchial smooth muscle Eukaryotic translation initiation factor 4E Short peptide CCAAT/enhancer binding protein 4E binding protein Mammalian target of rapamycin Upstream open reading frame |
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Snippet | Bronchial smooth muscle (BSM) cells of asthmatic patients have an impaired expression of CCAAT/enhancer binding protein (C/EBP) α, which is associated with... Background Bronchial smooth muscle (BSM) cells of asthmatic patients have an impaired expression of CCAAT/enhancer binding protein (C/EBP) α, which is... Bronchial smooth muscle (BSM) cells of asthmatic patients have an impaired expression of CCAAT/enhancer binding protein (C/EBP) alpha, which is associated with... |
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SubjectTerms | Allergy and Immunology Asthma Asthma - genetics Asthma - immunology Asthma - metabolism Bronchi - immunology Bronchi - metabolism bronchial smooth muscle cell hyperplasia C/EBPα Calreticulin - immunology Calreticulin - metabolism CCAAT-Enhancer-Binding Protein-alpha - biosynthesis CCAAT-Enhancer-Binding Protein-alpha - immunology Cell Proliferation Cells, Cultured Eukaryotic Initiation Factor-4E - immunology Eukaryotic Initiation Factor-4E - metabolism Heterogeneous-Nuclear Ribonucleoproteins - immunology Heterogeneous-Nuclear Ribonucleoproteins - metabolism Humans Interleukin-6 - biosynthesis Interleukin-6 - immunology messenger RNA translation Myocytes, Smooth Muscle - immunology Myocytes, Smooth Muscle - metabolism Protein Biosynthesis RNA, Messenger - immunology RNA, Messenger - metabolism |
Title | Impaired translation of CCAAT/enhancer binding protein α mRNA in bronchial smooth muscle cells of asthmatic patients |
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