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Regulation of lung inflammation by the LTC4 synthase pathway

Institution: University of California, San Diego
Investigator(s): Kenneth Serio, M.D.
Award Cycle: 1999 (Cycle 8) Grant #: 8KT-0126 Award: $225,000
Subject Area: Pulmonary Disease
Award Type: New Investigator Awards

Initial Award Abstract
Asthma is a prevalent lung disease, which affects about 10% of the population in the United States. Hospitalizations and deaths due to asthma have been observed to be increasing, despite the availability of new drugs for the treatment of this disease. In asthmatic patients, tobacco smoke exposure has been found to be associated with increased severity of disease and increased utilization of the health care system. In chronic obstructive pulmonary disease, a clear links has been established between this disease and tobacco smoke exposure.

Asthma and chronic obstructive pulmonary disease are caused by airway inflammation in the lung. This occurs, in part, due to the presence of inflammatory fats, called eukotrienes. The leukotrienes are produced by specific cells and the lung is known to be a rich source of these substances. How the leukotrienes are produced is not fully understood, but it appears that their production is normally tightly controlled by the body. The principal investigator will investigate how one enzyme in the leukotriene pathway, called LTC4 synthase, is regulated and what causes the cells to make more of this enzyme.

Sophisticated research methods will be used to study the control of the gene for the ETCH synthase enzyme. This gene appears to be very complex, but its function is probably controlled by specific factors within the cell. In addition, the effect of steroids, which are commonly used to treat asthma and chronic obstructive pulmonary disease, on this gene will be assessed. The research may provide insight into why tobacco smoke exposure appears to counteract the effect of steroids.

The knowledge of the control of this gene will allow more knowledge f the leukotriene pathway. The investigator hopes that understanding the leukotriene pathway will expand the knowledge of inflammation in the lung, which is relevant to understanding the effects of tobacco smoke exposure. The findings of the proposed work would, therefore, aid in the treatment of asthma and chronic obstructive pulmonary disease.

Identification of a novel transcriptional regulatory element important for the constitutive expression of the LTC4 synthase gene in the moncyte-like cell line, THP-1
Periodical: American Journal of Respiratory and Critical Care Medicine Index Medicus:
Authors: Serio KJ, Hodulik CR, Bigby TD ABS
Yr: 2000 Vol: 161 Nbr: A334 Abs: Pg: