The endocannabinoid system in asthma patients and the effect of cannabinoids in the modulation of inflammatory responseEsteves Pinto Kozmus, Carina (Avtor) Potočnik, Uroš (Mentor) AsthmaEndocannabinoid systemCannabinoidsInflammationMolecular geneticsAsthma is a chronic inflammatory condition characterised by intermittent and reversible airflow obstruction caused by inflammation, bronchospasm, and increased airway secretions. Questions about the endocannabinoid system’s function in asthma pathogenesis have arisen as evidence grows, demonstrating it is a native modulator of immune functions. The main goal of this study was to genetically characterise the endocannabinoid system in naive asthma patients and determine if there is a relationship between endogenous cannabinoids and their inflammatory response. We studied a case-control cohort of 353 patients with mild/moderate persistent asthma and 276controls. The mRNA expression levels of the selected genes were quantified in peripheral blood mononuclear cells (PBMCs) and N-acylethanolamines (NAEs) quantified from plasma samples. Our results revealed that the genes for CB1 (CNR1) andCB2 (CNR2), along with genes for the enzymes NAPE-PLD (NAPEPLD), Abhd4(ABHD4) and MAGL (MGLL) were up-regulated in asthma patients and associated with their clinical and inflammatory condition. In addition, two of the genotyped polymorphisms located in the CNR2 gene were also associated with worse clinical symptoms. Palmitoylethanolamide (PEA) levels were lower and significantly different between allergic asthma patients and the control group and associated with worse clinical symptoms. Furthermore, our findings indicate that asthma patients with highCNR1mRNA expression levels at the time of diagnosis, treated with LTA, have better treatment response, while asthma patients with highCNR1mRNA expression levels, treated with ICS, had worse treatment response. Long-term ICS or LTRA therapy reduced mRNA expression ofCNR1together withIL4andIL5.It is evident from these findings that the endocannabinoid system plays a role in asthma, but it is not possible to determine whether this up-regulation is a cause or a result of the condition. Nonetheless, our findings add to a better understanding of the endocannabinoid system’s significance in asthma pathogenesis.20212021-11-25 10:11:37Doktorsko delo/naloga80951sl