1,8-Cineol inhibits nuclear translocation of NF-魏B p65 and NF-魏B-dependent transcriptional activity

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• 作者：Johannes F.-W. Greiner ; Janine M眉ller ; Marie-Theres Zeuner ; Stefan Hauser ; Thorsten Seidel ; Christin Klenke ; Lena-Marie Grunwald ; Timo Schomann ; Darius Widera ; Holger Sudhoff ; Barbara Kaltschmidt ; Christian Kaltschmidt
• 关键词：1 ; 8-Cineol ; NF-魏B ; Human cell lines ; PBMCs ; Inflammation ; Inflammatory diseases
• 刊名：Biochimica et Biophysica Acta (BBA)/Molecular Cell Research
• 出版年：December, 2013
• 年：2013
• 卷：1833
• 期：12
• 页码：2866-2878
• 全文大小：2354 K

文摘

Natural plant-derived products are commonly applied to treat a broad range of human diseases, including cancer as well as chronic and acute airway inflammation. In this regard, the monoterpene oxide 1,8-cineol, the active ingredient of the clinically approved drug Soledum庐, is well-established for the therapy of airway diseases, such as chronic sinusitis and bronchitis, chronic obstructive pulmonary disease and bronchial asthma. Although clinical trials underline the beneficial effects of 1,8-cineol in treating inflammatory diseases, the molecular mode of action still remains unclear.

Here, we demonstrate for the first time a 1,8-cineol-depending reduction of NF-魏B-activity in human cell lines U373 and HeLa upon stimulation using lipopolysaccharides (LPS). Immunocytochemistry further revealed a reduced nuclear translocation of NF-魏B p65, while qPCR and western blot analyses showed strongly attenuated expression of NF-魏B target genes. Treatment with 1,8-cineol further led to increased protein levels of I魏B伪 in an IKK-independent matter, while FRET-analyses showed restoring of LPS-associated loss of interaction between NF-魏B p65 and I魏B伪. We likewise observed reduced amounts of phosphorylated c-Jun N-terminal kinase 1/2 protein in U373 cells after exposure to 1,8-cineol. In addition, 1,8-cineol led to decreased amount of nuclear NF-魏B p65 and reduction of its target gene I魏B伪 at protein level in human peripheral blood mononuclear cells.

Our findings suggest a novel mode of action of 1,8-cineol through inhibition of nuclear NF-魏B p65 translocation via I魏B伪 resulting in decreased levels of proinflammatory NF-魏B target genes and may therefore broaden the field of clinical application of this natural drug for treating inflammatory diseases.