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Inflammatory compounds:role in tobacco-related lung disease

Institution: University of California, San Diego
Investigator(s): Timothy Bigby, M.D.
Award Cycle: 1998 (Cycle 7) Grant #: 7RT-0097 Award: $447,367
Subject Area: Cancer
Award Type: Research Project Awards
Abstracts

Initial Award Abstract
Cigarette smoke is known to cause damage to the lungs of people who smoke and to those around them. One of the ways it does this is by causing inflammation of the breathing tubes (the airways) of the lung. How smoking does this is not known for sure. We do know that some types of fats can cause inflammation of the breathing tubes and an cause many of the symptoms seen in patients who have smoking-related lung disease: namely cough, shortness of breath, wheezing, and phlegm.

This proposal will carefully study how these inflammatory fats get made. The parts of the cell that make these inflammatory fats, the enzymes, appear to be carefully regulated. We will study how one enzyme responsible for making a very important inflammatory fat, called leukotriene C4, is regulated and what causes the cell to make more of this enzyme.

We hope that, through this work, we will better understand smoking-related lung disease and will be able to develop better treatments for patients with smoking-related lung disease.
Publications

Transforming growth factor beta increases leukotriene C4 synthase expression in the monocyte-like cell line, THP-1
Periodical: Journal of Immunology Index Medicus:
Authors: Riddick CA, Serio KJ, Hodulik DJ, Regan MS, Ring WL, Bigby TD ART
Yr: 1999 Vol: 162 Nbr: Abs: Pg: 1101-1107

Regulation of leukotriene C4 synthase gene expression by Sp1 and Sp3 in mononuclear phagocytes
Periodical: American Journal of Respiratory and Critical Care Medicine Index Medicus:
Authors: Serio KJ, Hodulik CR, Bigby TD ABS
Yr: 1999 Vol: 159 Nbr: A642 Abs: Pg:

Regulation of expression of the 5-lipoxy genase pathway
Periodical: Clinical Reviews in Allergy and Immunology Index Medicus:
Authors: Bigby TD ART
Yr: 1999 Vol: 14 Nbr: Abs: Pg: 43-58

SP1 and Sp3 function as key regulators of leukotriene C4 synthase gene expression in the monocyte-like cell line THP-1
Periodical: American Journal of Respiratory Cell and Molecular Biology Index Medicus:
Authors: Serio KJ, Hodulik CR, Bigby TD ART
Yr: 2000 Vol: 23 Nbr: Abs: Pg: 234-240

Perspective: the leukotriene C4 synthase gene and asthma
Periodical: American Journal of Respiratory Cell and Molecular Biology Index Medicus:
Authors: Bigby TD ART
Yr: 2000 Vol: 23 Nbr: Abs: Pg: 273-276

Regulation of leukotriene C4 synthase gene expression by Sp1 and Sp3 in mononuclear phagocytes
Periodical: American Journal of Respiratory and Critical Care Medicine Index Medicus:
Authors: Serio KJ, Hodulik CR, Bigby TD ART
Yr: 1999 Vol: 159 Nbr: A642 Abs: Pg:

Identification of a novel transcriptional regulatory element important in the constitutive expression of the LTC4 synthase gene in the monocyte-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: Abs: A334 Pg:

The yin and the yang of 5-lipoxygenase pathway activation
Periodical: Molecular Pharmacology Index Medicus:
Authors: Bigby TD ART
Yr: 2002 Vol: 62 Nbr: Abs: Pg: 200 - 202

A single base pair A to C substitution at - 366 in the promoter region of the LTC4 synthase gene is associated with decreased expression in vitro.
Periodical: American Journal of Respiratory and Critical Care Medicine Index Medicus:
Authors: Jamil SM, Hodulik CR, Serio KJ, and Bigby TD ART
Yr: 2000 Vol: 161 Nbr: A762 Abs: Pg: