Objectives Inflammation can be endogenously modulated by the cholinergic anti-inflammatory pathway via calcium (Ca2+)-permeable alpha-7 nicotinic acetylcholine receptor (α7nAChR) ion channel expressed in immune cells. α7nAChR 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 α7nAChR antagonists. The effects of choline and KYNA on COX-2 enzyme, PGE2, TNFα, NF-κB and intracellular Ca2+ levels were analyzed. Results LPS-induced COX-2 expression, PGE2 TNFα and NF-κB levels were decreased with choline treatment while intracellular calcium levels via α7nAChRs 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.

Introduction Medulloblastoma is the most common pediatric central nervous tumor of high malignancy that has been classified into both histological subtypes and molecular subgroups by the 2016 World Health Organization classification. However, there is a still need to understand the genomic characteristics and predict the clinical course. The aim of the study is to investigate the significance of the methylation profiles in molecular subclassification and precision medicine of the disease. Methods The study enrolled 47 pediatric medulloblastoma patients. DNA methylation levels of KLF4, SPINT2, RASSF1A, EZH2, ZIC2, and PTCH1 genes were analyzed using methylation-specific pyrosequencing. The significance of the statistical relationship between methylation profiles and clinicopathological parameters including molecular subgroups and histological subtypes, the status of metastasis, and event-free survival were analyzed. Results DNA methylation analysis demonstrated that KLF4, PTCH1, and ZIC2 hypermethylation were associated with the SHH-activated subgroup, whereas both SPINT2 and RASSF1A hypermethylation were associated with metastatic disease. EZH2 gene was not methylated in any of the samples. Conclusion We think that customized DNA methylation profiling may be a useful tool in the molecular subclassification of pediatric medulloblastoma and a potential technical approach in precision medicine.