The non-antibiotic macrolide EM900 attenuates HDM and poly(I:C)-induced airway inflammation with inhibition of macrophages in a mouse model.
Animals
Anti-Inflammatory Agents
/ pharmacology
Asthma
/ drug therapy
Bronchoalveolar Lavage Fluid
/ cytology
Cytokines
/ immunology
Disease Models, Animal
Erythromycin
/ analogs & derivatives
Female
Lung
/ drug effects
Macrophages, Alveolar
/ drug effects
Mice, Inbred BALB C
Poly I-C
Pyroglyphidae
/ immunology
Virus Diseases
/ drug therapy
Asthma
EM900
HDM
Macrolide
Macrophage
Journal
Inflammation research : official journal of the European Histamine Research Society ... [et al.]
ISSN: 1420-908X
Titre abrégé: Inflamm Res
Pays: Switzerland
ID NLM: 9508160
Informations de publication
Date de publication:
Jan 2020
Jan 2020
Historique:
received:
15
08
2019
accepted:
03
12
2019
revised:
22
11
2019
pubmed:
11
12
2019
medline:
22
10
2020
entrez:
11
12
2019
Statut:
ppublish
Résumé
Macrolides have been reported to reduce the exacerbation of severe asthma. The aim of this study was to clarify the effects and mechanisms of EM900, a non-antibiotic macrolide, on allergic airway inflammation. Mice were sensitized and challenged by house dust mite (HDM), then exposed to polyinosinic-polycytidylic acid (poly(I:C)) as a model of asthma complicated with viral infection. Mice were administered with EM900. Airway inflammation was assessed from inflammatory cells in bronchoalveolar lavage fluid (BALF) and cytokines in lung tissues. Lung interstitial macrophages were counted by flow cytometry. Cytokine production, phosphorylation of NF-κB, and p38 in macrophages were examined by ELISA and western blotting. Counts of cells in BALF and concentrations of IL-13, IL-5, RANTES, IL-17A, and MIP-2 were significantly decreased by EM900 compared to those without EM900. Percentages of lung interstitial macrophages were significantly decreased with EM900. Concentrations of IL-6, RANTES, and MIP-2 induced by HDM and poly(I:C) were significantly suppressed by EM900 through the suppression of NF-κB and p38 phosphorylation in macrophages. HDM and poly(I:C)-induced airway inflammation is attenuated by EM900 with the inhibition of lung interstitial macrophages. Clinical use of EM900 is expected, because EM900 has inhibitory effects against airway inflammation without inducing bacterial drug resistance.
Identifiants
pubmed: 31820024
doi: 10.1007/s00011-019-01302-3
pii: 10.1007/s00011-019-01302-3
pmc: PMC6942021
doi:
Substances chimiques
(8R,9S)-8,9-dihydro-6,9-epoxy-8,9-anhydropseudoerythromycin A
0
Anti-Inflammatory Agents
0
Cytokines
0
Erythromycin
63937KV33D
Poly I-C
O84C90HH2L
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
139-151Références
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