An enzyme that inactivates the inflammatory mediator leukotriene b4 restricts mycobacterial infection.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Tobin, DM; Roca, FJ; Ray, JP; Ko, DC; Ramakrishnan, L

Published Date

  • 2013

Published In

Volume / Issue

  • 8 / 7

Start / End Page

  • e67828 -

PubMed ID

  • 23874453

Pubmed Central ID

  • PMC3708926

Electronic International Standard Serial Number (EISSN)

  • 1932-6203

Digital Object Identifier (DOI)

  • 10.1371/journal.pone.0067828


  • eng

Conference Location

  • United States