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

被引:33
作者
Ayaz, Gulsen [1 ]
Halici, Zekai [1 ]
Albayrak, Abdulmecit [1 ]
Karakus, Emre [2 ]
Cadirci, Elif [1 ]
机构
[1] Ataturk Univ, Dept Pharmacol, Fac Med, TR-25240 Erzurum, Turkey
[2] Ataturk Univ, Dept Pharmacol & Toxicol, Fac Vet Med, TR-25240 Erzurum, Turkey
关键词
5-HT7; LPS; Sepsis; LP44; SB269970; NF-KAPPA-B; NECROSIS FACTOR; SEROTONIN; EXPRESSION; SEPSIS; HYPERRESPONSIVENESS; ACTIVATION; RESPONSES;
D O I
10.1007/s10528-016-9769-2
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 mu g/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 mu g/ml) (2-4 h); VI LPS+ antagonist 10(-9) M (2-4 h). In molecular analyses, we determined increased TNF-alpha, IL-1 beta, NF-kappa B, and 5-HT7 mRNA expressions in rat lung tissues and increased TNF-alpha, 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.
引用
收藏
页码:34 / 47
页数:14
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