Cigarette smoke off a key enzyme in the respiratory tract, the regulatory response against inflammation, according to data from the University of Alabama at Birmingham published online Science Express.
UAB researchers say smoke inhibits an enzyme called leukotriene A4 Hydrolase (LTA4H), which leads to their failure in his work to close the white blood cells after a successful fight against inflammation.
The group said that the study revealed previously unknown substrate LTA4H called proline glycine-proline (PGP). In the normal response to inflammation, the role of PGP is a set of neutrophils - white blood cells - that rush to the scene and attack the cause of inflammation. When work is completed, LTA4H steps to disable the PGP, in turn, the cessation of recruitment of neutrophils and ending defensive body.
"We found, however, that cigarette smoke prevents LTA4H, preventing him from closing PGP", said Edwin J. Blalock, Ph.D., lead author and professor at UAB Division of Pulmonary Allergy and intensive care. "The continued presence of PGP funds continued response of neutrophils, an infinite loop that supports the chronic inflammation."
Blalock said PGP is a biomarker of several lung diseases, chronic inflammation of the functions, such as chronic obstructive pulmonary disease (COPD) and cystic fibrosis.
The study also details the dual role played by LTA4H in suppression or promotion of inflammation. When contained in the chamber, LTA4H has proinflammatory work, creating an agent knows how to leukotriene B4 (LTB4), which, like PGP, calls in neutrophils, if necessary. However, when LTA4H is outside the cell (when the camera is in his death, for example), its role becomes an anti-1, as it works to suppress PGP and the end of the inflammatory reaction of the organism.
"This dual role has been poorly understood until we have defined the PGP", said Blalock. "This could have important implications for the development of new anti-inflammatory drugs intended LTA4H".
Blalock said that, because too many LTB4 may contribute to chronic inflammation, pharmaceutical manufacturers are studying potential drugs prevent LTA4H, thereby reducing the amount of LTB4. Blalock said he believes that the approach needs to be reviewed.
"Drugs in the design, thus reducing LTB4 by closing LTA4H", he said. "But we now know that LTA4H beneficial role in reducing the PGP.
"While preventing LTB4 can be good, while the ability to block LTA4H degradation PGP hit a target, and can make the situation worse."
This research was supported by grants from National Heart, Lung, and Blood Institute, one of the National Institutes of Health.
Blalock has collaborated with Robert Snelgrove, Ph.D., Imperial College London, as well as with colleagues from the University of Montevallo (Montevallo, Ala.), Birmingham Veterans Affairs Medical Center, Inc. "Medical Center, Lung, Gregory Fleming James Cystic Fibrosis Center and Department of Pediatrics.
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