Discussion
Autophagy plays an important role in immunity,and defects in autophagy can induce inflammation and inflammatory diseases[19- 21].Accumulating evidence shows that autophagy also modulates immune responses by regulating apoptosis.Autophagy inhibits apoptosis of marginal zone B cells in the spleen and promotes the TⅠ-Ⅱimmune response[22].Autophagy not only regulates damage-associated molecular pattern(DAMP)release and degradation,but also is negatively regulated by DAMPs[23].Autophagy also plays a role in atherosclerosis by mediating the apoptosis of macrophages,smooth muscle cells and vascular endothelial cells[24].
Macrophages locate throughout the body and are beneficial in anti-microbial and anti-tumor immune responses,metabolism and obesity,allergy and asthma,tumorigenesis,autoimmunity,atherosclerosis,fibrosis and wound healing.Increasing the number of macrophages has been shown to induce bone osteopetrosis,atherosclerosis and the development of tumorigenesis[25,26].Macrophage cell death is a double-edged sword in an inflammatory response.In some cases,apoptosis leads to disease,such as in atherosclerotic plaque development,but in other cases it is beneficial,such as in the protection of macrophages against pathogen infection[27].Excessive apoptosis of macrophages leads to immunosuppression and contributes to a higher risk of occurrence of secondary infection[28].In this study,we observed that OSCs increased apoptosis of RAW264.7 cells,indicating that OSCs may function in immunity via regulating macrophage apoptosis.(https://www.daowen.com)
OSCs have been shown to enhance the function of the immune system by stimulating certain cell types,such as macrophages,lymphocytes,natural killer cells,dendritic cells,and eosinophils.They also contribute to the treatment and prevention of pathologies such as obesity,metabolic syndrome,cardiovascular disorders,immunoglobulin production,phagocytosis and macrophage activation,but the molecular mechanisms have yet to be clarified[5,29,30].We found that SAC,DADS and DTS increased macrophage apoptosis by enhancing Caspase 3 activity,suggesting a potential mechanism for how garlic modulates immunity.
Our results provide strong evidence that autophagy modulates the immune response by regulating apoptosis.Apoptosis of macrophages affects atherosclerotic plaque development and response to pathogen infection.OSCs also play roles in immunomodulation and inflammation.We found that SAC,DADS and DTS induced autophagy in RAW264.7 cells by inhibiting m TOR phosphorylation activity.They also decreased the apoptotic rate of macrophages with increased autophagy.The key autophagy gene ATG5 has been reported to play an important role in the regulation of apoptosis,and the anti-ap optotic effect of SAC,DADS and DTS was attenuated after knockdown of ATG5[31- 33].Hence,the protective effect of SAC,DADSand DTSagainst apoptosis is due to their effects on autophagy.Because autophagy has cytoprotective effects,downregulation of autophagy in macrophages to promote apoptosis may be a potential therapeutic target to improve immunity.