Evaluation of 5-HT7 Receptor Trafficking on In Vivo and In Vitro Model of Lipopolysaccharide (LPS)-Induced Inflammatory Cell Injury in Rats and LPS-Treated A549 Cells

Abstract

This study aimedto investigate the effects of the 5-HT7 receptor agonist (LP44) and antagonist (SB269970) on LPS-induced in vivo tissue damage and cell culture by molecular methods. This study was conducted in two steps. For in vivo studies, 24 female rats were divided into four groups. Group I: healthy; II (2nd h): LPS 5mg/kg administered intraperitoneally (i.p.); III (4th h): LPS 5mg/kg administered i.p.; IV (8th h): LPS 5mg/kg administered i.p. For in vitro studies, we used the A549 cell line. Groups: I control (healthy) (2-4h); II LPS: 1µg/ml E. Coli O55:B5 strain (2-4h); III agonist (LP44) 10-9 M (2-4h); IV antagonist (SB269970) 10-9 M (2-4h); V LPS+agonist 10-9 M (LP44 1µg/ml) (2-4h); VI LPS+antagonist 10-9 M (2-4h). In molecular analyses, we determined increased TNF-α, IL-1β, NF-κB, and 5-HT7 mRNA expressions in rat lung tissues and increased TNF-α, iNOS, and 5-HT7 mRNA expressions in the A549 cell line. In in vitro parameters, LP44 agonist administration-related decrease was observed. Our study showed that lung 5-HT7 receptor expression is increased in LPS-induced endotoxemia. All this data suggest that 5-HT7 receptor overexpression is an important protective mechanism during LPS-induced sepsis-related cell damage.