[HTML][HTML] An Enzyme That Inactivates the Inflammatory Mediator Leukotriene B4 Restricts Mycobacterial Infection

DM Tobin, FJ Roca, JP Ray, DC Ko, L Ramakrishnan - PloS one, 2013 - journals.plos.org
PloS one, 2013journals.plos.org
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 …
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.
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