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.
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