Roles of the toll-like receptor 4-induced interleukin-18 in acute lung injury induced by seawater drowning
10.3760/cma.j.issn.1009-6906.2018.03.003
- VernacularTitle:Toll样受体4诱导的白细胞介素-18在小鼠海水淹溺性急性肺损伤中的作用研究
- Author:
Yanfang LIU
1
;
Yan GU
;
Jie ZHU
;
Yanfeng WU
Author Information
1. 海军军医大学附属长海医院病理科,上海,200433
- Publication Type:Journal Article
- Keywords:
Interleukin-18;
Toll like receptor 4;
Seawater drowning;
Acute lung injury;
Therapy
- From:
Chinese journal of nautical medicine and hyperbaric medicine
2018;25(3):142-145
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the roles of interleukin-18 (IL-18) in acute lung injury induced by seawater drowning (SW-ALI).Methods Following development of the SW-ALI model,24 male C57 mice were randomly divided into 4 groups,each consisting of 6 animals.Then,lung,serum and bronchoalveolar lavage fluid (BALF) samples of each group were collected at 0,4,8 and 12 h time points.The mRNA expression levels of IL-18 and toll-like receptor 4 (TLR4) were detected by quantitative PCR.The expression of IL-18 in serum and BALF was detected by enzyme linked immunosorbent assay (ELISA).To investigate the effect of TLR4 on the secretion of IL-18,8 TLR4-/-mice were chosen and were designated as the TLR4-/-group,meanwhile another 8 normal C57 mice were selected and were designated as the WT group to develop the SW-ALI model,and 12 hours later,IL-18 level was detected by ELISA.Then,12 male mice were randomly divided into 3 groups:the normal control group,the SW-ALI group and the SW-ALI + IL-18BP group.The animals in the control group were left there intact,but the animals in the SW-ALI + IL-18BP group were injected in tail vein with IL-18BP at a dosage of 0.5 mg/kg,4 and 8 hours after development of the SW-ALI model,and the animals in the SW-ALI group were injected with the same amount of PBS,but without IL-18BP injection after development of the SW-ALI model.Twenty-four hours later,HE staining was performed for the detection of pathological changes in the lungs of the mice of each group.Results Following development of the SW-ALI model and with the elapse of time,the mRNA expression of IL-18 and TLR4 in the lungs and the level of IL-18 in serum and BALF gradually increased.As compared with that of the wild C57 mice,the secretion of IL-18 in the TLR4-deficient mice obviously reduced,after development of the SW-ALI model.The IL-18-binding protein in IL-18BP could compromise IL-18 and obviously inhibit lung inflammation induced by SW-ALI.Conclusions From the mouse SW-ALI model,we can see that the expression of IL-18 would be increased with the progress of the disease and was associated with the activation of TLR4.IL-18BP treatment can alleviate lung inflammation response caused by SW-ALI.
