In mice, silica exposure increases expression of ICAM-1 on lung (alveolar/interstitial) macrophages. It is unclear how silica increases ICAM-1 on exposed macrophages and the inflammatory mediators involved in increased ICAM-1 expression. By understanding the regulation of silica induced ICAM-1 expression in lung macrophages, it may be possible to modulate the expression of this adhesion molecule, alter cell activation and suppress lung injury. Using mouse macrophages in vitro, this proposal will test the following hypothesis: INFLAMMATORY CYTOKINES AND REACTIVE OXYGEN/NITROGEN SPECIES PARTICIPATE IN THE REGULATION OF ICAM-1 ON MOUSE MACROPHAGES EXPOSED TO PARTICLES IN VITRO.
Two specific aims will be addressed:
SPECIFIC AIM I. To determine in mouse macrophages (MH-S, RAW 264.7), the effect of particles on ICAM-1 expression in association with other markers of cell activation (cytokines, reactive oxygen/nitrogen species, transcription factor activation).
SPECIFIC AIM II. To determine the role of identified cytokines and/or reactive oxygen/nitrogen species in silica-induced ICAM-1 expression. The effect of either specific anti-cytokine antibodies or inhibitors of reactive oxygen/nitrogen species will be determined by analyzing their effect on transcription factor activation and any resulting changes in ICAM-1 mRNA or protein expression.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32HL010360-01
Application #
6140054
Study Section
Lung Biology and Pathology Study Section (LBPA)
Project Start
2000-09-01
Project End
Budget Start
2000-09-01
Budget End
2001-08-31
Support Year
1
Fiscal Year
2000
Total Cost
$42,882
Indirect Cost
Name
University of Connecticut
Department
Pharmacology
Type
Schools of Pharmacy
DUNS #
City
Storrs-Mansfield
State
CT
Country
United States
Zip Code
06269