Alantolactone Enhances the Phagocytic Properties of Human Macrophages and Modulates Their Proinflammatory Functions.
Front Pharmacol. 2020 ;11:1339. Epub 2020 Sep 3. PMID: 33013371
Aim of the Study: Phagocytosis is a crucial element of innate immune defense involved in bacterial killing. The aim of our study was to evaluate the influence of alantolactone on phagocytosis and cytokines release by THP1-derived macrophages. We assessed whether antimicrobial compound alantolactone (a sesquiterpene lactone present in.) is able to stimulate immune functions of macrophages by increase ofuptake, phagosome acidification and further stimulation of phago-lysosomes formation. Simultaneously, we tested influence of alantolactone on cytokines/chemokines production and p65 NF-κB concentration. The activity of alantolactone was compared with clarithromycin at concentration 20 µM.
Methods: The cytotoxicity of alantolactone as well asuptake, pH of phagosomes and phago-lysosomes fusion were analysed with flow cytometry. Reactive oxygen species and superoxide production were evaluated spectrophotometrically. The efficiency of phagocytosis was evaluatedquantifying viable bacteria (CFU). The effect on p65 protein concentration and cytokine production by macrophages were measured by enzyme-linked immunosorbent assay (ELISA).
Results: Alantolactone enhanced phagocytosisincrease ofuptake, acidification of phagosomes, and later stimulation of phago-lysosomes fusion. Alantolactone treatment resulted in ROS and superoxide production decrease. Furthermore, alantolactone inhibited production of pro-inflammatory cytokines TNF-α, IL-1β, IL-6, and IL-8 as well as decreased p65 concentration, the subunit responsible for NF-κB activation and cytokine production and simultaneously stimulated release of anti-inflammatory mediators (IL-10 and TGF-β).
Conclusion: Results of our study indicate that alantolactone enhances clearance of, and simultaneously modulates immune response, preventing collateral damage of the surrounding tissues. Considering the importance of phagocytosis in the pathogen killing, alantolactone may have a great potential as the supportive treatment ofinfections. Furtherstudies are warranted to confirm this hypothesis.