Carbocisteine attenuates TNF-alpha-induced inflammation in human alveolar epithelial cells in vitro through suppressing NF-kappaB and ERK1/2 MAPK signaling pathways.

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Wang W, Guan WJ, Huang RQ, Xie YQ, Zheng JP, Zhu SX, Chen M, Zhong NS

Carbocisteine attenuates TNF-alpha-induced inflammation in human alveolar epithelial cells in vitro through suppressing NF-kappaB and ERK1/2 MAPK signaling pathways.

Acta Pharmacol Sin. 2016 May;37(5):629-36. doi: 10.1038/aps.2015.150. Epub 2016 Mar 21.

PubMed ID
26997568 [ View in PubMed
]
Abstract

AIM: We previously proven that carbocisteine, a conventional mucolytic drug, remarkably reduced the rate of acute exacerbations and improved the quality of life in the patients with chronic obstructive pulmonary disease. In this study we investigated the mechanisms underlying the anti-inflammatory effects of carbocisteine in human alveolar epithelial cells in vitro. METHODS: Human lung adenocarcinoma cell line A549 was treated with TNF-alpha (10 ng/mL). Carbocisteine was administered either 24 h prior to or after TNF-alpha exposure. The cytokine release and expression were measured using ELISA and qRT-PCR. Activation of NF-kappaB was analyzed with Western blotting, immunofluorescence assay and luciferase reporter gene assay. The expression of ERK1/2 MAPK signaling proteins was assessed with Western blotting. RESULTS: Carbocisteine (10, 100, 1000 mumol/L), administered either before or after TNF-alpha exposure, dose-dependently suppressed TNF-alpha-induced inflammation in A549 cells, as evidenced by diminished release of IL-6 and IL-8, and diminished mRNA expression of IL-6, IL-8, TNF-alpha, MCP-1 and MIP-1beta. Furthermore, pretreatment with carbocisteine significantly decreased TNF-alpha-induced phosphorylation of NF-kappaB p65 and ERK1/2 MAPK, and inhibited the nuclear translocation of p65 subunit in A549 cells. In an NF-kappaB luciferase reporter system, pretreatment with carbocisteine dose-dependently inhibited TNF-alpha-induced transcriptional activity of NF-kappaB. CONCLUSION: Carbocisteine effectively suppresses TNF-alpha-induced inflammation in A549 cells via suppressing NF-kappaB and ERK1/2 MAPK signaling pathways.

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