Enhancement of the antimycobacterial activity of macrophages by ajoene
| Autor: | Dam Go, Junghwan Lee, Soo-Na Cho, Yun-Ji Lim, Chang-Hwa Song, Seon-Hwa Kim, Ji-Ae Choi |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
MAP Kinase Signaling System medicine.drug_class Immunology Antimycobacterial Microbiology Cell Line Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Ajoene Autophagy medicine Animals Humans Disulfides Molecular Biology chemistry.chemical_classification antimycobacterial activity Reactive oxygen species Chemistry Kinase Macrophages Endoplasmic reticulum apoptosis Mycobacterium tuberculosis Original Articles Cell Biology Endoplasmic Reticulum Stress ER stress response Anti-Bacterial Agents Cell biology RAW 264.7 Cells 030104 developmental biology Infectious Diseases Apoptosis Sulfoxides 030220 oncology & carcinogenesis Unfolded protein response Mitogen-Activated Protein Kinases Reactive Oxygen Species |
| Zdroj: | Innate Immunity |
| ISSN: | 1753-4267 1753-4259 |
| Popis: | Ajoene, a garlic-derived sulfur-containing compound, has broad-spectrum antimicrobial activity. To assess the potential of ajoene for treating tuberculosis (TB), we determined whether it induces the stress response of the endoplasmic reticulum (ER), which plays an important role in TB. We showed that ajoene stimulation induced the production of ER stress sensor molecules and reactive oxygen species (ROS) levels. Ajoene-induced ROS production was dependent on c-Jun N-terminal kinase (JNK) activation. Interestingly, the inhibition of JNK activity and suppression of ROS production reduced ajoene-induced CHOP production in macrophages. Because ER stress activates autophagy, the activation of which suppresses the growth of mycobacteria, we investigated the ajoene-induced production of autophagy-related factors, including LC3-II, P62 and Beclin-1. As expected, ajoene treatment increased the levels of these factors in RAW 264.7 cells. Remarkably, the total amount of Mycobacterium tuberculosis (Mtb) H37Rv was significantly reduced in ajoene-treated RAW 264.7 cells. The treatment of macrophages with ajoene resulted in the activation of JNK, induction of ROS synthesis and accumulation of ROS, possibly leading to the activation of ER stress and autophagy. These results reveal the mechanism of the antimycobacterial effects of ajoene against Mtb H37Rv. Our findings might facilitate the development of novel therapies for patients with TB. |
| Databáze: | OpenAIRE |
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