Melaleuca alternifolia Induces Heme Oxygenase-1 Expression in Murine RAW264.7 Cells through Activation of the Nrf2-ARE Pathway
| Autor: | Nicholas S. Kirkby, Tsu-Chung Chang, Shih-Yu Lee, Po-Yu Chen, Jung-Chun Lin, Ching-Huei Ou |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Lipopolysaccharide Macrophage NF-KAPPA-B HUMAN MONOCYTES Anti-Inflammatory Agents Gene Expression Nitric Oxide Synthase Type II Integrative & Complementary Medicine Monocytes chemistry.chemical_compound Mice MACROPHAGES Heme biology General Medicine 11 Medical And Health Sciences Melaleuca CANCER Cell biology Blot Biochemistry Melaleuca alternifolia Inflammation Mediators Life Sciences & Biomedicine Signal Transduction NF-E2-Related Factor 2 p38 mitogen-activated protein kinases HO-1 Nitric Oxide Nrf2 MECHANISMS 03 medical and health sciences TERPINEN-4-OL Medicine General & Internal INFLAMMATION Tea Tree Oil General & Internal Medicine Animals Humans Electrophoretic mobility shift assay RNA Messenger Transcription factor Science & Technology Terpenes AMPK PATHWAY Membrane Proteins biology.organism_classification Heme oxygenase 030104 developmental biology RAW 264.7 Cells Complementary and alternative medicine chemistry Complementary & Alternative Medicine KEAP1-NRF2 PATHWAY Heme Oxygenase-1 |
| Popis: | Melaleuca alternifolia concentrate (MAC) is the refined essential oil of the Australian native plant Melaleuca alternifolia. MAC has been reported to suppress the production of pro-inflammatory cytokines in both murine RAW264.7 macrophages and human monocytes stimulated with lipopolysaccharide (LPS). However, the mechanisms involved in this effect remain unclear. This study aims to delineate the molecular mechanisms that drive the anti-inflammatory activity of MAC and its active component, terpinen-4-ol, in macrophages. The effects of MAC on RAW264.7 cells were studied using western blotting, real-time PCR, an electrophoretic mobility shift assay (EMSA), and NF-[Formula: see text]B luciferase reporter assays. Our results showed that MAC significantly increased both the mRNA and protein levels of heme oxygenase-1 (HO-1) via p38 and JNK MAPK activation. In addition, we showed that MAC significantly increased the activation and nuclear translocation of NF-E2-related factor 2 (Nrf2), a key transcription factor regulating HO-1 induction. MAC was also associated with significant inhibition of iNOS expression, NO production, and NF-[Formula: see text]B activation. HO-1 was required for these anti-inflammatory effects as tin protoporphyrin IX (SnPPIX), an HO-1 inhibitor, abolished the effects of MAC on LPS-induced iNOS, NO, and NF-[Formula: see text]B activation. Our results indicate that MAC induces HO-1 expression in murine macrophages via the p38 MAPK and JNK pathways and that this induction is required for its anti-inflammatory activity. |
| Databáze: | OpenAIRE |
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