title: Regulatory mechanism of pyrrolidine dithiocarbamate is mediated by nuclear factor-κB and inhibits neutrophil accumulation in ARDS mice.
abstract: The aim of the present study was to investigate the regulatory mechanism of nuclear factor (NF)-κB on polymorphonuclear neutrophil (PMN) accumulation and the inflammatory response in lung tissues with acute respiratory distress syndrome (ARDS), as well as the therapeutic effect of pyrrolidine dithiocarbamate (PDTC). Mouse models of ARDS were established by intraperitoneal injection of lipopolysaccharide (LPS). BALB/c mice were divided into control, LPS and PDTC + LPS groups. The expression of PMN adhesion molecules, CD11b/CD18 and intercellular adhesion molecule-1 (ICAM-1), were detected by immunohistochemistry, while the protein expression levels of NF-κB p65 in the lung tissue were analyzed by western blot analysis. In addition, flow cytometry was used to investigate the apoptosis rate of PMNs in the bronchoalveolar fluid, and the expression levels of interleukin (IL)-1β, IL-8 and tumor necrosis factor (TNF)-α and myeloperoxidase (MPO) activity were also determined. Following an intraperitoneal injection of LPS, alveolar septum rupture, pulmonary interstitial hyperemia and PMN infiltration in the alveolar was observed. The protein expression of p65 in the pulmonary cytoplasm decreased, while the expression of p65 in the nucleus increased. The levels of IL-8, IL-1β and TNF-α increased and the high expression status was maintained for 24 h. As the time increased, CD11b/CD18 and ICAM-1 expression increased, as well as MPO activity, while the apoptosis of PMNs was delayed. Compared with the LPS group, the expression of p65 in the pulmonary cytoplasm and the PMN apoptosis rate increased following PDTC intervention, while the expression of p65 in the nucleus decreased, as well as the expression levels of the cytokines and MPO activity. Therefore, PDTC reduced the production of inflammatory cytokines via the NF-κB pathway, which reduced the activation of PMNs in the lung tissue and promoted PMN apoptosis.
authors.affiliation: Department of Pulmonary Medicine, Qilu Hospital, Shandong University, Jinan, Shangdong 250012, P.R. China ; Department of Pulmonary Medicine, The Thrid Affiliated Hospital of Liaoning Medical University, Jinzhou, Liaoning 121001, P.R. China ; Department of Pulmonary Medicine, The Fifth Affiliated Hospital of Zunyi Medical University Zhuhai, Zhuhai, Guangdong 519100, P.R. China.
authors.forename: Hongman
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Pulmonary Medicine, Qilu Hospital, Shandong University, Jinan, Shangdong 250012, P.R. China.
authors.forename: Lisheng
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Pulmonary Medicine, Qilu Hospital, Shandong University, Jinan, Shangdong 250012, P.R. China.
authors.forename: Jiping
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Pulmonary Medicine, The Thrid Affiliated Hospital of Liaoning Medical University, Jinzhou, Liaoning 121001, P.R. China.
authors.forename: Donghui
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Pulmonary Medicine, Qilu Hospital, Shandong University, Jinan, Shangdong 250012, P.R. China ; Department of Pulmonary Medicine, The Thrid Affiliated Hospital of Liaoning Medical University, Jinzhou, Liaoning 121001, P.R. China.
authors.forename: Ranran
authors.initials: R
authors.lastname: Guo
authors.affiliation: Department of Pulmonary Medicine, Qilu Hospital, Shandong University, Jinan, Shangdong 250012, P.R. China.
authors.forename: Junfei
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pulmonary Medicine, Qilu Hospital, Shandong University, Jinan, Shangdong 250012, P.R. China.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Gong
authors.affiliation: Department of Pulmonary Medicine, Qilu Hospital, Shandong University, Jinan, Shangdong 250012, P.R. China.
authors.forename: Tian
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Pulmonary Medicine, Qilu Hospital, Shandong University, Jinan, Shangdong 250012, P.R. China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pulmonary Medicine, Qilu Hospital, Shandong University, Jinan, Shangdong 250012, P.R. China.
authors.forename: Liang
authors.initials: L
authors.lastname: Dong
keywords: CD11b/CD18; acute respiratory distress syndrome; intercellular adhesion molecule-1; nuclear factor-κB; pyrrolidine dithiocarbamate