An enzyme that inactivates the inflammatory mediator leukotriene b4 restricts mycobacterial infection.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 23874453.
- Also identified by DOI 10.1371/journal.pone.0067828 and PMC identifier 3708926.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
While tuberculosis susceptibility has historically been ascribed to failed inflammation, it is now known that an excess of leukotriene A4 hydrolase (LTA4H), which catalyzes the final step in leukotriene B4 (LTB4) synthesis, produces a hyperinflammatory state and tuberculosis susceptibility. Here we show that the LTB4-inactivating enzyme leukotriene B4 dehydrogenase/prostaglandin reductase 1 (LTB4DH/PTGR1) restricts inflammation and independently confers resistance to tuberculous infection. LTB4DH overexpression counters the susceptibility resulting from LTA4H excess while ltb4dh-deficient animals can be rescued pharmacologically by LTB4 receptor antagonists. These data place LTB4DH as a key modulator of TB susceptibility and suggest new tuberculosis therapeutic strategies.
Medical subject headings
- Alcohol Oxidoreductases
- Leukotriene B4
- Mycobacterium Infections
- Tuberculosis