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Your search keyword '"Petit, Aurélie"' showing total 6 results
Start Over Author "Petit, Aurélie" Publisher european respiratory society
6 results on '"Petit, Aurélie"'

3. Cellular mechanisms underlying CCSP SNP association with chronic airway diseases

Author

Jennifer Bonini, Lucie Knabe, Jessica Varilh, Petit Aurélie, Arnaud Bourdin, Pascal Chanez, Isabelle Vachier, and Magali Taulan

Subjects
Therapeutic gene modulation, Transcription (biology), Wild type, Endogeny, Promoter, Transfection, respiratory system, Biology, Transcription factor, Gene, Molecular biology
Abstract

Club cell secretory protein (CCSP) is an endogenous anti-inflammatory product with a protective role in the respiratory tract. Impaired airway homeostasis in chronic bronchial diseases might be related to CCSP G38A polymorphism but the SNP-transcription relationship is not established. This study was to examine the influence of ccsp G38A polymorphism on CCSP expression and regulation. Vectors constructions (proximal promoter: 229bp; and distal promoter: 926bp) containing -38G wild type or the -38A variant were designed. Human bronchial BEAS-2B cells were transfected with these proximal or distal promoters, in presence/absence of cigarette smoke extract (CSE). Dual luciferase assay system reflected CCSP transcription levels. In parallel, dual transfections with candidate modulating transcription factors identified by in silico analysis using ConSite and TFSEARCH were conducted. No significant changes are induced by the -38G and -38A vectors in transiently transfected BEAS-2B cells. Cotransfection with Nkx2.1 significantly increased CCSP transcription. Interestingly, with proximal promoter only,-38A variant gene response to Nkx2.1 was higher than -38G wild type response. CSE decreased CCSP transcription. In depth-in silico analyzes identified two novel candidate transcription factors that could specifically bind to the G38A locus: Thing1E47 and p53. Our data indicate that two novel transcription factors and CSE could affect CCSP expression. Also, -38A variant CCSP gene modulation induced by Nkx2.1 is significant. Finding transcription factors that could restore normal levels of CCSP expression is of interest.

Published
2015

6. CCSP counterbalances airway epithelial-driven neutrophilic chemotaxis.

Author

Knabe L, Petit A, Vernisse C, Charriot J, Pugnière M, Henriquet C, Sasorith S, Molinari N, Chanez P, Berthet JP, Suehs C, Vachier I, Ahmed E, and Bourdin A

Subjects
Humans, Interleukin-8 metabolism, Interleukin-8 pharmacology, Neutrophils drug effects, Pulmonary Disease, Chronic Obstructive metabolism, Recombinant Proteins pharmacology, Smoking, Sputum cytology, Bronchioles pathology, Chemotaxis, Leukocyte, Neutrophils cytology, Pulmonary Disease, Chronic Obstructive pathology, Uteroglobin pharmacology
Abstract

Club cell secretory protein (CCSP) knockout mice exhibit increased airway neutrophilia, as found in chronic obstructive pulmonary disease (COPD). We therefore investigated whether treating COPD airway epithelia with recombinant human CCSP (rhCCSP) could dampen exaggerated airway neutrophilia.Control, smoker and COPD air-liquid interface (ALI) cultures exposed to cigarette smoke extract (CSE) were treated with and without rhCCSP. The chemotactic properties of the supernatants were assessed using Dunn chambers. Neutrophil chemotaxis along recombinant human interleukin 8 (rhIL8) gradients (with and without rhCCSP) was also determined. rhCCSP-rhIL8 interactions were tested through co-immunoprecipitation, Biacore surface plasmon resonance (SPR) and in silico modelling. The relationship between CCSP/IL8 concentration ratios in the supernatant of induced sputum from COPD patients versus neutrophilic airway infiltration assessed in lung biopsies was assessed.Increased neutrophilic chemotactic activity of CSE-treated ALI cultures followed IL8 concentrations and returned to normal when supplemented with rhCCSP. rhIL8-induced chemotaxis of neutrophils was reduced by rhCCSP. rhCCSP and rhIL8 co-immunoprecipitated. SPR confirmed this in vitro interaction (equilibrium dissociation constant=8 µM). In silico modelling indicated that this interaction was highly likely. CCSP/IL8 ratios in induced sputum correlated well with the level of small airway neutrophilic infiltration (r 2 =0.746, p<0.001).CCSP is a biologically relevant counter-balancer of neutrophil chemotactic activity. These different approaches used in this study suggest that, among the possible mechanisms involved, CCSP may directly neutralise IL8., Competing Interests: Conflict of interest: L. Knabe has nothing to disclose. Conflict of interest: A. Petit has nothing to disclose. Conflict of interest: C. Vernisse has nothing to disclose. Conflict of interest: J. Charriot has nothing to disclose. Conflict of interest: M. Pugnière has nothing to disclose. Conflict of interest: C. Henriquet has nothing to disclose. Conflict of interest: S. Sasorith has nothing to disclose. Conflict of interest: N. Molinari has nothing to disclose. Conflict of interest: P. Chanez has nothing to disclose. Conflict of interest: J-P. Berthet has nothing to disclose. Conflict of interest: C. Suehs has nothing to disclose. Conflict of interest: I. Vachier has nothing to disclose. Conflict of interest: E. Ahmed has nothing to disclose. Conflict of interest: A. Bourdin has nothing to disclose., (Copyright ©ERS 2019.)

Published
2019
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