Shikonin changes the lipopolysaccharide-induced expression of inflammation-related genes in macrophages
| Autor: | Hiromi Takano-Ohmuro, Tomohito Kakegawa, Yasukatsu Yuda, Lucia Satiko Yoshida |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Lipopolysaccharides Lipopolysaccharide Cell Gene Expression Inflammation Biology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Immune system Gene expression medicine Animals Humans GSK3B Innate immune system Macrophages EIF4E Anti-Inflammatory Agents Non-Steroidal Cell Differentiation Molecular biology 030104 developmental biology medicine.anatomical_structure chemistry 030220 oncology & carcinogenesis Molecular Medicine medicine.symptom Naphthoquinones |
| Zdroj: | Journal of natural medicines. 71(4) |
| ISSN: | 1861-0293 |
| Popis: | We aimed to find candidate molecules possibly involved in the anti-inflammatory activity of shikonin (active compound of "Shikon") by analyzing its effects on gene expression of lipopolysaccharide (LPS)-treated THP-1 macrophages. Polysome-associated mRNAs (those expected to be under translation: translatome) from cells treated with LPS alone (LPS: 5 µg/mL), shikonin alone (S: 100 nM), or LPS plus shikonin (LPSS) for 3 h were analyzed by DNA microarray followed by detection of enriched pathways/gene ontologies using the tools of the STRING database. Candidate genes in enriched pathways in the comparison of LPSS cells vs. LPS cells were analyzed by reverse-transcription quantitative real-time PCR (RT-qPCR; 1, 2, and 3 h). DNA microarray showed shikonin significantly influences gene expression. Gene expression changes between LPSS cells and LPS cells were compared to detect relevant proteins and/or mRNAs underlying its anti-inflammatory effects: shikonin downregulated pathways which were upregulated in LPS cells, for example, 'innate immune response'. Within changed pathways, three genes were selected for RT-qPCR analyses as key candidates influencing inflammatory responses: CYBA (component of the superoxide-generating Nox2 enzyme), GSK3B (controller of cell responses after toll-like receptor stimulation), and EIF4E (a key factor of the eukaryotic translation initiation factor 4F complex that regulates abundance of other proteins involved in immune functions). All three mRNAs were decreased at 2 h, and CYBA continued low at 3 h relative to LPS cells. Given that shikonin decreased the expression of CYBA gene of Nox2, in addition to the direct inhibition of the Nox2 activity that we have previously shown, it is suggested that one of its anti-inflammatory mechanisms could be attenuation of oxidative stress. |
| Databáze: | OpenAIRE |
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