TREM-1 and EP2 Effects on Chronic Inflammation and Aging

Chronic inflammation, a natural cause of aging, has recently emerged as playing a primary role in the pathogenesis of many degenerative diseases. A number of previous studies have provided evidence that the EP2 and TREM-1 receptors upregulate pro-inflammatory responses, through downstream signaling pathways. Additionally, knocking out these genes has shown to provide some protective effects against the consequences of several conditions thought to be related to chronic inflammation or the immune system. However, there is still a lot left to understand in terms of the mechanisms through which these protective effects occur, and how EP2 mice fare as they age. Therefore, this study sought to explore any immune system changes that could be quantified in EP2 and TREM-1 mice and the effects these had. Results are still exploratory in nature and in some cases inconclusive. However, clear evidence was found that TREM-1 reduces natural aging related bone loss and osteoporosis. Additionally, an upregulation in several pro-inflammatory markers and cytokines was discovered as expected. Interestingly, results appear to show this effect more strongly in young mice than aged mice, the opposite of what was predicted. This could indicate that in young mice EP2 is necessary to implement a pro-inflammatory response, but as they age other systems offer redundant inflammation. Finally, early results suggest that EP2 KO mutants have an increased number of, and larger, epithelial cell rest of Malassezs (ERMs). ERMs usually increase in number after a wound and are associated with higher inflammation. This suggests that mice could possibly be compensating for the loss of EP2 with ERMs. However, more work will need to be done to confirm these findings and determine what consequences this might have.