Ergosta-7,9(11),22-trien-3β-ol Attenuates Inflammatory Responses via Inhibiting MAPK/AP-1 Induced IL-6/JAK/STAT Pathways and Activating Nrf2/HO-1 Signaling in LPS-Stimulated Macrophage-like Cells
| Autor: | Wen-Jen Lin, Wen Tsong Hsieh, Yueh-Hsiung Kuo, Jing Gung Chung, Yi-Ping Huang, Te Chun Hsia, Jiann-Yeu Chen, Dar-Ren Chen, Yu Hsien Lin |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
MAPK/ERK pathway
MAPK/AP-1 signaling pathways Physiology Clinical Biochemistry RM1-950 Cordyceps militaris Biochemistry Article stat Ergosta-7 9(11) 22-trien-3β-ol (EK100) atomic force microscopy (AFM) Nrf2/ HO-1 signaling pathway Protein kinase A Molecular Biology Chemistry Activator (genetics) JAK-STAT signaling pathway Cell Biology IL-6/JAK/STAT signaling pathways anti-inflammatory response Cancer research STAT protein Tumor necrosis factor alpha Therapeutics. Pharmacology Janus kinase |
| Zdroj: | Antioxidants Volume 10 Issue 9 Antioxidants, Vol 10, Iss 1430, p 1430 (2021) |
| ISSN: | 2076-3921 |
| DOI: | 10.3390/antiox10091430 |
| Popis: | Chronic inflammation induces autoimmune disorders and chronic diseases. Several natural products activate nuclear factor erythroid 2-related factor 2 (Nrf2) signaling, attenuating inflammatory responses. Ergosta-7,9(11),22-trien-3β-ol (EK100) isolated from Cordyceps militaris showed anti-inflammatory and antioxidative activity, but those mechanisms are still unclear. This study is the first to investigate EK100 on antioxidant Nrf2 relative genes expression in LPS-stimulated macrophage-like cell lines. The results showed that EK100 reduced IL-6 (interleukin-6) and tumor necrosis factor-α production. EK100 also attenuated a mitogen-activated protein kinase/activator protein-1 (MAPK/AP-1) pathway and interleukin-6/Janus kinase/signal transducer and activator of transcription (IL-6/JAK/STAT) pathway in LPS-stimulated cells. Toll-like receptor 4 (TLR4) inhibitor CLI-095 and MAPK inhibitors can synergize the anti-inflammatory response of EK100 in LPS-stimulated cells. Moreover, EK100 activated Nrf2/HO-1 (heme oxygenase-1) signaling in LPS-stimulated murine macrophage-like RAW 264.7 cells, murine microglial BV2 cells, and human monocytic leukemia THP-1 cells. However, Nrf2 small interfering RNA (Nrf2 siRNA) reversed EK100-induced antioxidative proteins expressions. In conclusion, EK100 showed anti-inflammatory responses via activating the antioxidative Nrf2/HO-1 signaling and inhibiting TLR4 related MAPK/AP-1 induced IL-6/JAK/STAT pathways in the LPS-stimulated cells in vitro. The results suggest EK100 acts as a novel antioxidant with multiple therapeutic targets that can potentially be developed to treat chronic inflammation-related diseases. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|