Effects of kynurenic acid and choline on lipopolysaccharide-induced cyclooxygenase pathway

Abstract

Objectives: Inflammation can be endogenously modulated by the cholinergic anti-inflammatory pathway via calcium (Ca2+)-permeable alpha-7 nicotinic acetylcholine receptor (a7nAChR) ion channel expressed in immune cells. a7nAChR agonist choline and tryptophan metabolite kynurenic acid (KYNA) produces immunomodulatory effects. This study aimed to determine the effects of the choline and KYNA on the lipopolysaccharide (LPS)-induced cyclooxygenase (COX)-2 pathway.Methods: In vitro inflammation model was produced via LPS administration in macrophage cells. To determine the effective concentrations, choline and KYNA were applied with increasing concentrations and LPS-induced inflammatory parameters investigated. The involvement of nAChR mediated effects was investigated with the use of non-selective nAChR and selective a7nAChR antagonists. The effects of choline and KYNA on COX-2 enzyme, PGE(2), TNFa, NF-?B and intracellular Ca2+ levels were analyzed.Results: LPS-induced COX-2 expression, PGE(2) TNFa and NF-?B levels were decreased with choline treatment while intracellular calcium levels via a7nAChRs increased. KYNA also showed an anti-inflammatory effect on the same parameters. Additionally, KYNA administration increased the effectiveness of choline on these inflammatory mediators.Conclusions: Our data suggest a possible interaction between the kynurenine pathway and the cholinergic system on the modulation of LPS-induced inflammatory response in macrophages.