Induction of MUC5AC expression to Aspergillus fumigatus in airway epithelial cells and suppressive effects brought about macrolide antibacterial agents

Ref ID: 19610

Author:

K Hirano1*, K Izumikawa1, M Yoshida1, N Kaku2, K Takeda1, S Ide1, A Minematsu1, Y Harada2,
T Takazono1, K Kosai3, Y Morinaga2, S Kurihara3, S Nakamura1, Y Imamura1, M Tsukamoto3,
K Yanagihara2, T Tashiro4, S Kohno1

Author address:

1Department of Molecular Microbiology and Immunology, Nagasaki University Graduate School of
Biomedical Sciences, Nagasaki, Japan
2Department of Laboratory Medicine, Nagasaki University Hospital, Nagasaki, Japan
3Infection Control and Education Ce

Full conference title:

6th Advances Against Aspergillosis 2014

Abstract:

Purpose:
Pathology of chronic pulmonary aspergillosis has many parts which are not elucidated. It is thought
that local immunity of lungs is important to long-term colonization of Aspergillus spp. MUC5AC
is main mucin protein constituting airway mucus. It has been already reported that MUC5AC
production from the respiratory tract is stimulated by infection of Chlamydophila pneumoniae,
Haemophilus influenzae, Legionella pneumophila and Mycoplasma pneumonia. Mucus secretion
plays a role in host protection of mucosal surfaces against pathogens. However, excessive mucus
secretion affects mucociliary transport system and contributes chronic respiratory infectious disease.
Therefore we examined that induction of MUC5AC expression to Aspergillus fumigatus in airway
epithelial cells and suppressive effects brought about macrolide antibacterial agents.
Methods:
Airway epithelial cells (NCl-H292, ATCC® Number: In CRL-1848TM) were cultured in RPMI 1640
medium (GIBCO RPMI 1640). NCI-H292 cells were stimulated for 24 hours in the presence of the
A. fumigatus (5233, ATCC® Number: Culture of 13073TM) culturing supernatant. We regulated
concentration of culture supernatant adjustment with β -D glucan, from 100pg/ml to 1000pg/ml.
The concentrations of MUC5AC protein in culture supernatant were measured by ELISA. We used
lipopolysaccharide as a positive control to inhibition. As a control, cells were treated with culture
RPMI medium alone. Furthermore we added macrolide antibiotics (azithromycin or clarithromycin)
to NCI-H292 cells just before exposure to A. fumigatus culture supernatant, to determine the effect
on MUC5AC expression. Concentration of azithromycin and clarithromycin are used at 50μg/ml.
Results:
The level of secreted MUC5AC increased with culture supernatant of A. fumigatus addition in a
dose-dependent manner. MUC5AC protein levels were measured by ELISA and given in terms
of % above control. It resulted more than 200% above control at highest concentration stimulator.
Macrolide antibiotics reduced the level of secreted MUC5AC protein at 50μg/ml. This effect was
seen from 20μg/ml and dose-dependently. There was no difference in the inhibition MUC5AC
production between azithromycin and clarithromycin.
Conclusion:
Our experiments have demonstrated an effect of macrolides on mucin overproduction induced by
A. fumigatus culture supernatant stimulation of airway epithelial cells. Our findings suggest that
suppressive of excessive mucus secretion may be able to reduce colonization of A. fumigatus. It is
thought that the effect of the macrolide on pulmonary aspergillosis will have to examine it more in
future.
NOTE: THIS ABSTRACT HAS BEEN SELECTED FOR ORAL PRESENTATION.

Abstract Number: 135

Conference Year: 2014

Link to conference website: http://www.AAA2014.org

New link: NULL

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