Zhang, X.; Nickerson, R.; Burton, L.; Stueck, A.; Holbein, B.; Cheng, Z.; Zhou, J.; Lehmann, C. The Hydroxypyridinone Iron Chelator DIBI Reduces Bacterial Load and Inflammation in Experimental Lung Infection. Biomedicines2024, 12, 1452.
Zhang, X.; Nickerson, R.; Burton, L.; Stueck, A.; Holbein, B.; Cheng, Z.; Zhou, J.; Lehmann, C. The Hydroxypyridinone Iron Chelator DIBI Reduces Bacterial Load and Inflammation in Experimental Lung Infection. Biomedicines 2024, 12, 1452.
Zhang, X.; Nickerson, R.; Burton, L.; Stueck, A.; Holbein, B.; Cheng, Z.; Zhou, J.; Lehmann, C. The Hydroxypyridinone Iron Chelator DIBI Reduces Bacterial Load and Inflammation in Experimental Lung Infection. Biomedicines2024, 12, 1452.
Zhang, X.; Nickerson, R.; Burton, L.; Stueck, A.; Holbein, B.; Cheng, Z.; Zhou, J.; Lehmann, C. The Hydroxypyridinone Iron Chelator DIBI Reduces Bacterial Load and Inflammation in Experimental Lung Infection. Biomedicines 2024, 12, 1452.
Abstract
Iron plays a critical role in lung infections due to its function in the inflammatory immune response but also as an important factor for bacterial growth. Iron chelation represents a potential therapeutic approach to inhibit bacterial growth and pathologically increased pro-inflammatory mediator production. The present study was designed to investigate the impact of the iron chelator, DIBI, in murine lung infection induced by intratracheal Pseudomonas aeruginosa (strain PA14) administration. DIBI (80mg/kg) was given by intraperitoneal injection either as a single dose immediately after PA14 administration or a double dose (second dose 4 h after PA14 administration). The results showed that lung NF-κBp65 levels, as well as levels of various inflammatory cytokines (TNFα, IL-1β, IL-6) both in lung tissue and bronchoalveolar lavage fluid (BALF), were significantly increased 24h after PA14 administration. Single-dose DIBI did not affect the bacterial load or inflammatory response in the lungs or BALF. However, two doses of DIBI significantly decreased bacterial load, attenuated NF-κBp65 upregulation, reduced inflammatory cytokines production, and relieved lung tissue damage. Our findings support the conclusion that the iron chelator, DIBI, can reduce lung injury induced by P. aeruginosa, via its anti-bacterial and anti-inflammatory effects.
Keywords
Lung infection; Pseudomonas aeruginosa; Iron chelation; Inflammation
Subject
Biology and Life Sciences, Life Sciences
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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