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Obstructive Lung Diseases: COPD: Etiology |

Sodium Tanshinone IIA Sulfonate Inhibits Cigarette Smoke-Induced Airway Inflammation via Regulating Cystic Fibrosis Transmembrane Conductance Regulator-Mediated Pathway FREE TO VIEW

Defu Li; Ziyi Wang; Jian Wang; Nanshan Zhong; Zhen Long; Wenju Lu
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State Key Laboratory of Respiratory Diseases, Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou, China


Copyright 2016, American College of Chest Physicians. All Rights Reserved.


Chest. 2016;149(4_S):A352. doi:10.1016/j.chest.2016.02.367
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SESSION TITLE: COPD: Etiology

SESSION TYPE: Original Investigation Poster

PRESENTED ON: Saturday, April 16, 2016 at 11:45 AM - 12:45 PM

PURPOSE: To determined the role and signaling of CFTR in modulating cigarette smoke (CS)-induced COPD development.

METHODS: The COPD mouse model was established by cigarette smoke exposure and LPS. The STS intervention was given via atomization inhalation. Lung functions were assessed by using Buxco lung function measurement system. The Proinflammatory cytokines IL-6 and KC in BALF were assayed with ELISA. The lung tissue was subjected to H&E staining. Furthermore, the level of CFTR was determined by Western Blotting. 16HBE cells were used to evaluate the effects of STS on signaling change caused by cigarette smoke exposure (CSE). CSE was used to treat 16HBE cells with or without STS. The IL-6 and IL-8 level in cell culture medium were measured. The levels of CFTR, phosphorylated ERK1/2 and nucleic Nrf2 were determined. Then the effects of CFTR inhibitor inh-172 or ERK1/2 inhibitor PD98059 on Nrf2 nuclear translocation and IL-6 secretion, and the effects of small interfering RNA of Nrf2 (siNrf2) and Nrf2 agonist TBHQ on IL-6 secretion were assessed in CSE treated 16HBE cells.

RESULTS: Compared with untreated mice, CS exposure caused lung functions decline manifested by increases of value on TLC, FRC, Cchord, RI and decrease FEV100/FVC. The STS intervention inhibited the lung function decline. The lung tissue sections displayed the effects of STS on inhibiting the increases on the mean linear intercept. In BAL fluid, STS relieved the increase of inflammatory cells number and of IL-6 and KC level. In lung tissue, STS abolished the downregulation of CFTR caused by cigarette smoke exposure. In 16HBE cells, STS inhibited CFTR decrease, ERK1/2 phosphorylation, Nrf2 upregulation and nuclear translocation, and IL-6 and IL-8 secretion induced by CSE. However, STS could not reverse the enhancing effects of inh-172 pretreatment on ERK1/2 phosphorylation, Nrf2 nuclear translocation and IL-6 secretion induced by CSE.

CONCLUSIONS: The decreased expression of CFTR contributes to COPD development likely by augmenting ERK1/2-Nrf-2 mediated pro-inflammatory cytokine production. STS could protect CS-induced COPD development in a CFTR dependent manner.

CLINICAL IMPLICATIONS: These results indicate that STS could inhibit CS-induced COPD development by preventing CS-induced CFTR reduction, thus inhibiting Cl--ERK1/2-Nrf2 mediated pro-inflammatory cytokine production in airway epithelial cells.

DISCLOSURE: The following authors have nothing to disclose: Defu Li, Ziyi Wang, Jian Wang, Nanshan Zhong, Zhen Long, Wenju Lu

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