The effect of NF-κB on NLRP3 of lung tissue in rats with acute lung injury induced by phosgene
10.3760/cma.j.issn.1671-0282.2018.06.012
- VernacularTitle:核转录因子-KB参与光气吸入性肺损伤NLRP3炎性小体的表达
- Author:
Daikun HE
1
,
2
;
Yiru SHAO
;
Fangqing ZHOU
;
Lin ZHANG
;
Jie SHEN
Author Information
1. 201508 上海,复旦大学附属金山医院核化伤害应急救治中心
2. 复旦大学化学伤害急危重病研究中心
- Keywords:
Nuclear factor-kappa B (NF-κB);
Phosgene;
acute lung injury;
Pyrin domain-containing 3 (NLRP3) innammasome;
Inhalation;
pyroptosis;
Inflammation;
Pyrrolidinedithiocarbamic acid (PDTC)
- From:
Chinese Journal of Emergency Medicine
2018;27(6):624-630
- CountryChina
- Language:Chinese
-
Abstract:
Objective To observe the effect of signal transduction pathway of nuclear factor-kappa B (NF-κB) on Nod-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome and pyroptosis in rats with acute lung injury induced (ALI) by phosgene. Methods The rats were randomly(random number) divided into 3 groups: air exposure control group, phosgene exposure group and PDTC group with phosgene exposure after 100 mg/kg pyrrolidine dithiocarbamate (PDTC) administration. The specimens of serum, bronchoalveolar lavage fluid (BALF) and lung tissue were collected 6 h after exposure. Morphological changes were observed by HE staining. The expression of NLRP3 in the lung of three groups was detected by immunohistochemistry. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the expressions of NF-κB p65, NLRP3, ASC and caspase-1 mRNA in the lung tissue. NF-κB p65,NLRP3, ASC and caspase-1 protein levels in the lung tissue were quantified by Western blot. The concentrations of IL-1β, IL-18 and IL-33 in the serum and BALF were measured by enzyme-linked immunosorbent assay (ELISA). Pyroptosis was observed by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL). Results The model of phosgene-induced ALI was successfully established in rats. Morphological changes with inflammatory cell infiltration were observed in the lung tissues of phosgene group, in which NLRP3 positive cells also could be observed by immunohistochemical staining. The mRNA expressions and protein levels of NF-κB p65, NLRP3 and caspase-1 in lung tissues were significantly increased (P＜0.05) in phosgene group, compared with air control group. The mRNA expressions and protein levels of NF-κB p65,NLRP3 and caspase-1 in lung tissues were significantly decreased (P＜0.05) in PDTC group, compared with phosgene group. The IL-1β,IL-18 and IL-33 protein levels in serum and BALF were significantly increased (P＜0.05) in phosgene group, compared with air control group. The IL-1β,IL-18 and IL-33 protein levels in serum and BALF were significantly decreased (P＜0.05) in PDTC group, compared with phosgene group. TUNEL results showed that pyroptosis in the lung tissue obviously increased in phosgene group, while decreased in PDTC group. Conclusions NLRP3 inflammasome and lung cell pyroptosis were induced through NF-kB signal transduction pathway in rats with acute lung injury caused by phosgene inhalation. Blockade of NF-κB can alleviate acute lung injury by down-regulating the expression of NLRP3 inflammasome to inhibit pyroptosis.
