Chronic
inflammation, a process linked to increased oxidative stress, may induce many diseases. Whether
beta-carotene prevents
inflammation is unclear. Using phorbol-12-myristate-13-acetate (PMA)-stimulated HL-60 cells, we investigated the effects of 2 or 20 microM
beta-carotene on the inflammatory reaction of monocyte/macrophage-like cells and the modulation of 20 microM
quercetin or
naringenin, two
flavonoids, of the effects of
beta-carotene. The effects of
quercetin and
naringenin were compared with that of
alpha-tocopherol, a well-known
antioxidant. The stimulated HL-60 cells were also co-incubated with A549 cells to investigate the
DNA-damaging ability of the stimulated monocyte/macrophage-like cells on target cells. Our results showed that preincubation with 20 microM
beta-carotene significantly enhanced the release of two pro-inflammatory mediators,
interleukin-8 and
tumor necrosis factor-alpha, in PMA-stimulated HL-60 cells and slightly increased the
DNA-damaging ability of these cells. By contrast, 2 microM
beta-carotene had an inhibitory effect on the inflammatory reaction in PMA-stimulated cells. The higher dose of
beta-carotene also exerted pro-inflammatory effects in
lipopolysaccharide-stimulated RAW264.7 cells. Furthermore,
quercetin,
naringenin, and
alpha-tocopherol partly suppressed the pro-inflammatory effects of 20 microM
beta-carotene on PMA-stimulated HL-60 cells, and the suppressing effects of
quercetin and
naringenin were better than or similar to those of
alpha-tocopherol.
Quercetin also additively or synergistically enhanced the inhibitory effects of 2 microM
beta-carotene on the secretion of pro-inflammatory mediators and the
DNA-damaging ability of PMA-stimulated HL-60 cells. The mechanisms underlying the effect of the
flavonoids were associated with their
antioxidant activity and inhibition of the production of pro-inflammatory
cytokines. Our results urge consideration of the safety of
beta-carotene supplementation concerning effects on
inflammation and suggest that the interaction between
beta-carotene and
quercetin or
naringenin may alter the effects of
beta-carotene on the secretion of pro-inflammatory mediators.