Novel Role of the Endocannabinoid System & Prostaglandin-Glycerols on Cytokine Release in LPS-Activated Macrophages
Conference Year
2024
Abstract
Macrophages, an innate immune cell, release cytokines which are signaling molecules that activate and regulate the immune response. RAW246.7 macrophage-like cells activated by bacterial peptide lipopolysaccharide (LPS) express the enzyme cyclooxygenase-2 (COX-2). COX-2 metabolizes arachidonic acid (AA) and the endocannabinoid 2-arachidonoylglycerol (2- AG), resulting in the early formation of prostaglandins (PGs) as well as a latent release of prostaglandin-glycerols (PG-Gs), respectively. The role of PG-Gs during the immune response is unknown. Our study aims to answer the question of how PG-Gs affect cytokine release in LPS-activated macrophages. These lipids may be an effective target to reduce inflammation and prevent the activation of the adaptive immune response. Using a capture ELISA, we found that monocyte chemoattractant protein-1 (MCP-1) concentration is increased when PG-G synthesis is inhibited. MCP-1 is a cytokine that recruits other immune cells to the site of infection. The increase in MCP-1 concentration when PG-G formation is inhibited is indicative of PG-Gs’ role in immune response regulation. This research suggests a novel role of 2-AG and resultant PG-G synthesis on the immune response. This connection between the endocannabinoid system and the immune response demonstrates a potential for cannabinoid-targeted as well as cannabinoid-derived therapeutics.
Primary Faculty Mentor Name
Lawrence Marnett
Status
Undergraduate
Student College
College of Engineering and Mathematical Sciences
Program/Major
Biomedical Engineering
Primary Research Category
Life Sciences
Novel Role of the Endocannabinoid System & Prostaglandin-Glycerols on Cytokine Release in LPS-Activated Macrophages
Macrophages, an innate immune cell, release cytokines which are signaling molecules that activate and regulate the immune response. RAW246.7 macrophage-like cells activated by bacterial peptide lipopolysaccharide (LPS) express the enzyme cyclooxygenase-2 (COX-2). COX-2 metabolizes arachidonic acid (AA) and the endocannabinoid 2-arachidonoylglycerol (2- AG), resulting in the early formation of prostaglandins (PGs) as well as a latent release of prostaglandin-glycerols (PG-Gs), respectively. The role of PG-Gs during the immune response is unknown. Our study aims to answer the question of how PG-Gs affect cytokine release in LPS-activated macrophages. These lipids may be an effective target to reduce inflammation and prevent the activation of the adaptive immune response. Using a capture ELISA, we found that monocyte chemoattractant protein-1 (MCP-1) concentration is increased when PG-G synthesis is inhibited. MCP-1 is a cytokine that recruits other immune cells to the site of infection. The increase in MCP-1 concentration when PG-G formation is inhibited is indicative of PG-Gs’ role in immune response regulation. This research suggests a novel role of 2-AG and resultant PG-G synthesis on the immune response. This connection between the endocannabinoid system and the immune response demonstrates a potential for cannabinoid-targeted as well as cannabinoid-derived therapeutics.