halldorsson s, gudjonsson t, gottfredsson m, singh pk, gudmundsson gh, and baldursson o (2010) azithromycin maintains airway epithelial integrity during pseudomonas aeruginosa infection. am j respir cell mol biol 42:62–68.

Respuesta :

Study on use of ivermectin for Covid-19: Azithromycin maintains airway epithelial integrity during Pseudomonas aeruginosa infection.

The macrolide antibiotic azithromycin (azm) has been shown to improve lung function in CF patients without reducing bacterial counts in the lungs.

Overview:

Tight junctions (TJs) play an important role in maintaining the integrity of the bronchial epithelium. Patients with chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF) often suffer chronic infections with the opportunistic Gram-negative bacterium Pseudomonas aeruginosa, which produces several virulence factors, including rhamnolipids.

However, the mechanism of this effect is still debated. Azm was previously shown to increase transepithelial electrical resistance (TER) in bronchial epithelial cell lines.

In this study, we used an air-liquid interface model of human airway epithelium to measure changes in TER, TJ expression and structure after exposure to live Pseudomonas aeruginosa PAO1 and PAO1-Deltarhl, PAO1 mutants lacking rhlA and rhlB. Did. Enzyme for rhamnolipid production.

Additionally, cells were challenged with bacterial culture media conditioned by these strains, purified rhamnolipids, or synthetic 3O-C(12)-HSL. A virulence factor secreted by Pseudomonas aeruginosa reduced TER in the bronchial epithelium, causing TJ rearrangements and exposing the epithelium to further bacterial invasion. Pretreatment of bronchial epithelium with Azm attenuated this effect and promoted epithelial repair.

These data suggest that azm protects the bronchial epithelium during Pseudomonas aeruginosa infection independently of its antibacterial activity, partially explaining the beneficial results observed in clinical trials in patients with CF.

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