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
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This study aimed to 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 5 mg/kg administered intraperitoneally (i.p.); III (4th h): LPS 5 mg/kg administered i.p.; IV (8th h): LPS 5 mg/kg administered i.p. For in vitro studies, we used the A549 cell line. Groups: I control (healthy) (2–4 h); II LPS: 1 µg/ml E. Coli O55:B5 strain (2–4 h); III agonist (LP44) 10−9 M (2–4 h); IV antagonist (SB269970) 10−9 M (2–4 h); V LPS+agonist 10−9 M (LP44 1 µg/ml) (2–4 h); VI LPS+antagonist 10−9 M (2–4 h). 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.
Keywords5-HT7 LPS Sepsis LP44 SB269970
This study was supported by the TUBITAK 1001 project (TUBITAK-112S627) and was conducted in the pharmacology of the Faculty of Medicine at Ataturk University, 25240 Erzurum/Turkey. This study is a part of Master thesis of Gulsen AYAZ.
Compliance with Ethical Standards
Conflict of Interest
None of the authors has a commercial interest, financial interest, and/or other relationship with manufacturers of pharmaceuticals, laboratory supplies, and/or medical devices or with commercial providers of medically related services.
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