Macrolides protect against Pseudomonas aeruginosa infection via inhibition of inflammasomes

Li Chao Fan, Jie Lu Lin, Jia Wei Yang, Bei Mao, Hai Wen Lu, Bao Xue Ge, Augustine M.K. Choi, Jin Fu Xu

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Macrolides antibiotics have been effectively used in many chronic diseases, especially with Pseudomonas aeruginosa (P. aeruginosa) infection. The mechanisms underlying the therapeutic effects of macrolides in these diseases remain poorly understood. We established a mouse model of chronic lung infection using P. aeruginosa agar-beads, with azithromycin treatment or placebo. Lung injury, bacterial clearance, and inflammasome-related proteins were measured. In vitro, the inflammasomes activation induced by flagellin or ATP were assessed in LPS-primed macrophages with or without macrolides treatment. Plasma IL-18 levels were determined from patients who were diagnosed with bronchiectasis isolated with or without P. aeruginosa and treated with azithromycin for 3–5 days. Azithromycin treatment enhanced bacterial clearance and attenuated lung injury in mice chronically infected with P. aeruginosa, which resulted from the inhibition of caspase-1-dependent IL-1β and IL-18 secretion. In vitro, azithromycin and erythromycin inhibited NLRC4 and NLRP3 inflammasomes activation. Plasma IL-18 levels were higher in bronchiectasis patients with P. aeruginosa isolation compared with healthy controls. Azithromycin administration markedly decreased IL-18 secretion in bronchiectasis patients. The results of this study reveal that azithromycin and erythromycin exert a novel anti-inflammatory effect by attenuating inflammasomes activation, which suggests potential treatment options for inflammasome-related diseases.

Original languageEnglish (US)
Pages (from-to)L677-L686
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume313
Issue number4
DOIs
StatePublished - Oct 2017

Keywords

  • Immunomodulatory effects
  • Inflammasomes
  • Macrolides
  • Pseudomonas aeruginosa

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

Fingerprint Dive into the research topics of 'Macrolides protect against Pseudomonas aeruginosa infection via inhibition of inflammasomes'. Together they form a unique fingerprint.

Cite this