CHAC1 Is Differentially Expressed in Normal and Cystic Fibrosis Bronchial Epithelial Cells and Regulates the Inflammatory Response Induced by Pseudomonas aeruginosa
| العنوان: | CHAC1 Is Differentially Expressed in Normal and Cystic Fibrosis Bronchial Epithelial Cells and Regulates the Inflammatory Response Induced by Pseudomonas aeruginosa |
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| المؤلفون: | Léa Perra, Viviane Balloy, Tobias Foussignière, Didier Moissenet, Hortense Petat, Imran N. Mungrue, Lhousseine Touqui, Harriet Corvol, Michel Chignard, Loic Guillot |
| المساهمون: | Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Louisiana State University (LSU), Institut Pasteur [Paris], Mucoviscidose et bronchopathies chroniques : biopathologie et phénotypes cliniques (EA 2511), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5), Service de Pneumologie pédiatrique [CHU Trousseau], CHU Trousseau [APHP], MC received a grant from the French cystic fibrosis nonprofit organizations Vaincre La Mucoviscidose and Gregory Lemarchal. LP received a Ph.D. fellowship from the French cystic fibrosis nonprofit organization Vaincre La Mucoviscidose., Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Saint-Antoine [APHP], CHU Cochin [AP-HP]-Université Paris Descartes - Paris 5 (UPD5), Service de Pneumologie Pédiatrique [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut Pasteur [Paris] (IP) |
| المصدر: | Frontiers in Immunology Frontiers in Immunology, Frontiers, 2018, 9, pp.2823. ⟨10.3389/fimmu.2018.02823⟩ Frontiers in Immunology, Vol 9 (2018) Frontiers in Immunology, 2018, 9, pp.2823. ⟨10.3389/fimmu.2018.02823⟩ |
| بيانات النشر: | HAL CCSD, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | Adult, Male, 0301 basic medicine, lcsh:Immunologic diseases. Allergy, Small interfering RNA, Immunology, Bronchi, Inflammation, medicine.disease_cause, Cystic fibrosis, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, cystic fibrosis, 03 medical and health sciences, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, medicine, Humans, Immunology and Allergy, Pseudomonas Infections, Original Research, Aged, bronchial epithelium, Lung, biology, Chemistry, Pseudomonas aeruginosa, Epithelial Cells, Middle Aged, medicine.disease, Molecular biology, 3. Good health, ChaC glutathione-specific γ-glutamylcyclotransferase 1, 030104 developmental biology, medicine.anatomical_structure, Real-time polymerase chain reaction, Gene Expression Regulation, A549 Cells, Apoptosis, inflammation, biology.protein, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, medicine.symptom, lcsh:RC581-607, ER stress, gamma-Glutamylcyclotransferase, Flagellin |
| الوصف: | International audience; In cystic fibrosis (CF), Pseudomonas aeruginosa (Pa) colonizes the lungs, leading to chronic inflammation of the bronchial epithelium. ChaC glutathione-specific γ-glutamylcyclotransferase 1 (CHAC1) mRNA is differentially expressed in primary human airway epithelial cells from bronchi (hAECBs) from patients with CF and healthy patients at baseline and upon infection with Pa. CHAC1 degrades glutathione and is associated with ER stress and apoptosis pathways. In this study, we examined the roles of CHAC1 in the inflammatory response and apoptosis in lung epithelial cells. First, we confirmed by reverse transcription quantitative polymerase chain reaction that CHAC1 mRNA was overexpressed in hAECBs from patients without CF compared with the expression in hAECBs from patients with CF upon Pa (PAK strain) infection. Moreover, the Pa virulence factors LPS and flagellin were shown to induce CHAC1 expression in cells from patients without CF. Using NCI-H292 lung epithelial cells, we found that LPS-induced CHAC1 mRNA expression was PERK-independent and involved ATF4. Additionally, using CHAC1 small interfering RNA, we showed that reduced CHAC1 expression in the context of LPS and flagellin stimulation was associated with modulation of inflammatory markers and alteration of NF-κB signaling. Finally, we showed that Pa was not able to induce apoptosis in NCI-H292 cells. Our results suggest that CHAC1 is involved in the regulation of inflammation in bronchial cells during Pa infection and may explain the excessive inflammation present in the respiratory tracts of patients with CF. |
| اللغة: | English |
| تدمد: | 1664-3224 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a775bf42700f5c5375290066efded6f5Test https://hal.sorbonne-universite.fr/hal-01977256/file/fimmu-09-02823.pdfTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....a775bf42700f5c5375290066efded6f5 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 16643224 |
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