Immunomodulatory activity of betulinic acid by producing pro-inflammatory cytokines and activation of macrophages
2003
Yun, Yunha | Han, Shinha | Park, Eunjung | Yim, Dongsool | Lee, Sookyeon | Lee, Chong-Kil | Cho, Kyunghae | Kim, Kyungjae
Betulinic acid (BA), a pentacyclic triterpene isolated fromLycopus lucidus, has been reported to be a selective inducer of apoptosis in various human cancer and shown anti-inflammatory and immunomodulatory properties. We postulated that BA modulates the immunomodulatory properties at least two groups of protein mediators of inflammation, interlukin-1β (IL-1β) and the tumor necrosis factor-a (TNF-α) on the basis of the critical role of the monocytes and tissue macrophages in inflammatory and immune responses. TNF-α and IL-1β were produced by BA in a dose dependent manner at concentration of 0.625 and 10 μg/mL. The production of NO associated withiNOS was inhibited when treated with LPS at the concentration of 2.5 to 20 μg/mL of BA whereas COX-2 expression was decreased at 2.5 to 20 μg/mL. These modulations of inflammatory mediators were examined in LPS-stimulated RAW 264.7 cells and peritoneal macrophages. The morphology of macrophage was also examined and enhanced surface CD 40 molecule was expressed when treated BA at 0.625–5 ¼g/mL with or without LPS. Furthermore, BA (20 μg/mL) enhanced apoptosis by producing DNA ladder in the RAW 264.7 cells. Our results indicated that BA induced activation of macrophage and pro-inflammatory cytokines. This may provide a molecular basis for the ability of BA to mediate macrophage, suppress inflammation, and modulate the immune response.
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