The role of Prostaglandin E2 in alcohol-related inflammation in Drosophila melanogaster

Introduction

Alcohol consumption is a leading risk factor for premature mortality and disability. Alcohol consumption is known to activate pro-inflammatory signalling pathways that affect the production of prostaglandins (PGs) and reactive oxygen species (ROS). The mechanisms through which alcohol can alter PG synthesis are not fully understood. Drosophila melanogaster (fruit flies) is an established model system for studying alcohol-related behaviours and neuronal responses, but limited studies have utilised this model for elucidating alcohol-related inflammatory processes. In Drosophila, the Peroxinectin-like (PXT) and Cardinal (Cd) genes are believed to encode for putative cyclo-oxygenase-like enzymes and be responsible for PG synthesis, including PGE₂. The aim of this study is to understand the effect of alcohol consumption on PGE₂ levels in relation to inflammatory processes and addictive behaviours.

Methods

The development of tolerance was measured in Drosophila by measuring the time taken by half a cohort of flies to be sedated by ethanol vapours (ST50). An increase in ST50 following repeated ethanol exposures on consecutive days indicates development of tolerance. The level of PGE₂ was measured in homogenates of fly heads and bodies using an ELISA Kit (Cayman) in wild-type, PXT and Cd mutant flies with and without exposure to 2mM aspirin (a cyclo-oxygenase inhibitor).

Results and Conclusion

All Drosophila species examined developed tolerance. but their sensitivity to ethanol varied. Ethanol caused a different effect on PGE₂ production in different fly species (wild type and mutants); additionally, aspirin had a different capacity to alter the ethanol effect on PGE₂ production and the development of tolerance. These results, thus, provide evidence that the inflammatory process and addiction-related behaviours are interlinked and support the use of Drosophila as a tool for evaluating these mechanisms.