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

Tobin, David M

Roca, Francisco J

Ray, John P

Ko, Dennis C

Ramakrishnan, Lalita

Dheda, Keertan

United States

2015-12-18T01:03:05Z

2013

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.

http://www.ncbi.nlm.nih.gov/pubmed/23874453

PONE-D-13-12057

1932-6203

https://hdl.handle.net/10161/11197

eng

Public Library of Science (PLoS)

PLoS One

10.1371/journal.pone.0067828

Alcohol Oxidoreductases

Amino Acid Sequence

Animals

Humans

Inflammation

Leukotriene B4

Molecular Sequence Data

Mycobacterium Infections

Receptors, Leukotriene B4

Sequence Alignment

Tuberculosis

Zebrafish

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

Journal article

Tobin, David M|0000-0003-3465-5518

Ko, Dennis C|0000-0002-0113-5981

http://www.ncbi.nlm.nih.gov/pubmed/23874453

e67828

7

Basic Science Departments

Clinical Science Departments

Duke

Immunology

Medicine

Molecular Genetics and Microbiology

School of Medicine

Published online

8