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Cigarette smoke may contribute to lung inflammation through a new chemical pathway
Date:9/2/2010

BIRMINGHAM, Ala. Cigarette smoke shuts off a key enzyme in airways that regulates the body's response to inflammation, according to findings from the University of Alabama at Birmingham published online today at Science Express.

The UAB researchers say smoke inhibits the enzyme, called Leukotriene A4 Hydrolase (LTA4H), causing it to fail in its job of shutting down white blood cells following a successful response to inflammation.

The team says the research study identified a previously unknown substrate of LTA4H called proline-glycine-proline (PGP). In a normal response to inflammation, PGP's role is to recruit neutrophils white blood cells that rush to the scene and attack the cause of the inflammation. When the job is over, LTA4H steps in to shut off PGP, in turn halting the recruitment of neutrophils and ending the body's defensive stand.

"We found, however, that cigarette smoke inhibited LTA4H, preventing it from shutting down PGP," said J. Edwin Blalock, Ph.D., senior author and professor in the UAB Division of Pulmonary, Allergy and Critical Care Medicine. "A continued presence of PGP means a continued response of neutrophils, a never-ending cycle that supports chronic inflammation."

Blalock said PGP is a biomarker for several lung diseases that feature chronic inflammation, such as chronic obstructive pulmonary disease (COPD) and cystic fibrosis.

The study also details a dual role played by LTA4H in suppressing or encouraging inflammation. When contained within a cell, LTA4H has a pro-inflammatory job, generating an agent know as Leukotriene B4 (LTB4), which, much like PGP, calls in the neutrophils when required. However, when LTA4H is found outside of the cell (when the cell it resides in dies, for example) its role switches to an anti-inflammatory one, as it works to suppress PGP and end the body's inflammatory response.

"This dual role was poorly understood until we identified PG
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Contact: Bob Shepard
bshep@uab.edu
205-934-8934
University of Alabama at Birmingham
Source:Eurekalert

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