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ROLE OF ALVEOLAR MACROPHAGE IN OMEGA-3 FATTY ACID AMELIORATION OF SILICA-TRIGGERED AUTOIMMUNITY.

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Principal Investigator: Pestka, James J
Institute Receiving Award Michigan State University
Location East Lansing, MI
Grant Number R01ES027353
Funding Organization National Institute of Environmental Health Sciences
Award Funding Period 01 Jun 2017 to 31 Oct 2027
DESCRIPTION (provided by applicant): Summary: "Role of Alveolar Macrophage in Omega-3 Fatty acid Amelioration of Silica-Triggered Autoimmunity” While heredity is a primary predisposing factor for autoimmunity, cumulative exposures to environmental factors such as toxic stressors and diet greatly impact latency and severity autoimmune diseases such as lupus. Our goal is to understand how lupus triggering by an ubiquitous environmental toxicant can be prevented by dietary modulation of cellular lipids. This goal is predicated on preliminary studies revealing that 1)airway exposure to crystalline silica, a recognized autoimmune disease risk factor, triggers early onset of systemic autoimmunity and glomerulonephritis in the lupus-prone female NZBWF1 mouse and 2)supplementing their diets with the omega-3 fatty acid docosahexaenoic acid (DHA), a well-known dietary supplement extracted from cold-water fish, dose-dependently blocks this triggering. Here, we will employ in vitro, ex vivo, and in vivo approaches to test the hypothesis that DHA consumption prevents silica- triggered autoimmunity by suppressing inflammatory mediator production, death, and self-antigen release in alveolar macrophages of NZBWF1 mice. Revealing DHA mechanisms against silica- triggered lupus will bring novel insights into how respiratory toxicants initiate lupus and subsequent flaring via lung as well as how manipulating cellular lipids through diet can be exploited to prevent environmental triggering of human autoimmune disease.
Science Code(s)/Area of Science(s) Primary: 53 - Autoimmunity
Secondary: -
Publications No publications associated with this grant
Program Officer Michael Humble
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