Search

Your search keyword '"Chakir, Jamila"' showing total 347 results
Start Over Author "Chakir, Jamila"
347 results on '"Chakir, Jamila"'

5. MicroRNA-155-5p Differentially Regulates IL-13Rα1 and IL-13Rα2 Expression and Signaling Driving Abnormal Lung Epithelial Cell Phenotype in Severe Asthma.

Author

Klein, Martin, Gagnon, Pierre-Alexandre, Salem, Mabrouka, Rouabhia, Mahmoud, and Chakir, Jamila

Subjects
LUNGS, EPITHELIAL cells, PHENOTYPES, WESTERN immunoblotting, ASTHMA, ASTHMATICS, ADRENERGIC beta agonists, GENE amplification
Abstract

MicroRNA (miR)-155-5p increases in innate and adaptive immune cells in response to IL-13 and is associated with the severity of asthma. However, little is known about its role in airway structural cells. Bronchial epithelial cells (BECs) isolated from healthy donors and patients with severe asthma were stimulated with IL-13. miR-155-5p expression and release were measured by real-time (RT)-PCR in BECs and in their derived exosomes. Modulation of miR-155-5p in BECs was performed using transfection of miR-155-5p inhibitor and mimic. IL-13 receptor α1 (IL-13Rα1), IL-13Rα2, MUC5AC, IL-8, and eotaxin-1 expression was measured by RT-PCR and Western blot analysis. The BEC repair process was assessed by a wound-healing assay. IL-13Rα1 and IL-13Rα2 expression and downstream pathways were evaluated by Western blot analysis. A dual luciferase assay was used to identify miR-155-5p target genes associated with IL-13R signaling. BECs from patients with severe asthma showed increased expression and exosomal release of miR-155-5p at baseline with amplification by IL-13 stimulation. BECs from patients with asthma expressed more IL-13Rα1 and less IL-13Rα2 than those from healthy donors, and IL-13Rα1 but not IL-13Rα2 induced miR-155-5p expression under IL-13 stimulation. miR-155-5p overexpression favored MUC5AC, IL-8, and Eotaxin-1 through the IL-13Rα1/SOCS1/STAT6 pathway while delaying the repair process by downregulating IL-13Rα2/MAPK14/c-Jun/c-fos signaling. The dual luciferase assay confirmed that miR-155-5p modulates both IL-13R pathways by directly targeting SOCS1, c-fos, and MAPK14. miR-155-5p is overexpressed in BECs from patients with severe asthma and regulates IL-13Rα1 and IL-13Rα2 expression and signaling, favoring expression of mucin- and eosinophil-related genes to the detriment of airway repair. These results show that miR-155-5p may contribute to airway epithelial cell dysfunction in patients with severe asthma. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

6. Dysregulated invertebrate tropomyosin–dectin-1 interaction confers susceptibility to allergic diseases

Author

Gour, Naina, Lajoie, Stephane, Smole, Ursula, White, Marquitta, Hu, Donglei, Goddard, Pagé, Huntsman, Scott, Eng, Celeste, Mak, Angel, Oh, Sam, Kim, Jung-Hyun, Sharma, Annu, Plante, Sophie, Salem, Ikhlass Haj, Resch, Yvonne, Xiao, Xiao, Yao, Nu, Singh, Anju, Vrtala, Susanne, Chakir, Jamila, Burchard, Esteban G, Lane, Andrew P, and Wills-Karp, Marsha

Subjects
Biomedical and Clinical Sciences, Immunology, Lung, Genetics, Asthma, 2.1 Biological and endogenous factors, Inflammatory and immune system, Animals, Cells, Cultured, Disease Susceptibility, Female, Humans, Lectins, C-Type, Mice, Mice, Knockout, Polymorphism, Single Nucleotide, Tropomyosin, Clinical sciences
Abstract

The key factors underlying the development of allergic diseases-the propensity for a minority of individuals to develop dysfunctional responses to harmless environmental molecules-remain undefined. We report a pathway of immune counter-regulation that suppresses the development of aeroallergy and shrimp-induced anaphylaxis. In mice, signaling through epithelially expressed dectin-1 suppresses the development of type 2 immune responses through inhibition of interleukin-33 (IL-33) secretion and the subsequent recruitment of IL-13-producing innate lymphoid cells. Although this homeostatic pathway is functional in respiratory epithelial cells from healthy humans, it is dramatically impaired in epithelial cells from asthmatic and chronic rhinosinusitis patients, resulting in elevated IL-33 production. Moreover, we identify an association between a single-nucleotide polymorphism (SNP) in the dectin-1 gene loci and reduced pulmonary function in two cohorts of asthmatics. This intronic SNP is a predicted eQTL (expression quantitative trait locus) that is associated with reduced dectin-1 expression in human tissue. We identify invertebrate tropomyosin, a ubiquitous arthropod-derived molecule, as an immunobiologically relevant dectin-1 ligand that normally serves to restrain IL-33 release and dampen type 2 immunity in healthy individuals. However, invertebrate tropomyosin presented in the context of impaired dectin-1 function, as observed in allergic individuals, leads to unrestrained IL-33 secretion and skewing of immune responses toward type 2 immunity. Collectively, we uncover a previously unrecognized mechanism of protection against allergy to a conserved recognition element omnipresent in our environment.

Published
2018

28. AP-1 overexpression impairs corticosteroid inhibition of collagen production by fibroblasts isolated from asthmatic subjects

Author

Jacques, Eric, Semlali, Abdelhabib, Boulet, Louis Philippe, and Chakir, Jamila

Subjects
Asthma -- Risk factors, Asthma -- Genetic aspects, Asthma -- Research, Messenger RNA -- Physiological aspects, Messenger RNA -- Research, Transcription factors -- Physiological aspects, Transcription factors -- Research, Transforming growth factors -- Physiological aspects, Transforming growth factors -- Research, Biological sciences
Abstract

Asthma is characterized by airway remodeling associated with an increase in the deposition of ECM proteins such as type I collagen. These components are mainly produced by fibroblasts. Inhaled corticosteroids are considered the cornerstone of asthma therapy. Despite substantial evidence as to the anti-inflammatory action of corticosteroids, their effect on controlling ECM protein deposition in the airways is not completely understood. This study determined the effect of dexamethasone (Dex) on collagen production by bronchial fibroblasts derived from asthmatic and healthy subjects. Expression of procollagen mRNA in fibroblasts from asthmatics and normal controls was determined by quantitative PCR. Regulation of the procollagen-[[alpha].sub.1] promoter was evaluated by transient transfections. Transforming growth factor-[beta] (TGF-[beta]) protein expression was determined by ELISA. Protein expression of glucocorticoid receptor (GR) and interaction with activator protein-1 (AP-1), a collagen regulatory transcription factor, was assessed by Western blots, coimmunoprecipitations, and EMSA. AP-1 overexpression was performed by transient transfection using c-Fos/c-Jun expression plasmids. Dex signifcantly downregulated procollagen production and promoter activity in normal fibroblasts but had no effect on asthmatic fibroblasts. AP-1 and GR interaction increased after Dex stimulation in asthmatic fibroblasts. AP-1 overexpression in control fibroblasts abrogated collagen gene response to Dex. These results show that Dex failed to reduce collagen production in fibroblasts from asthmatic subjects. This impaired response may be related to AP-1 overexpression in these cells. asthma; airway remodeling; transforming growth factor-[beta]; glucocorticoid receptor doi: 10.1152/ajplung.00360.2009.

Published
2010

Catalog

Books, media, physical & digital resources
See catalog results