Luteolin suppresses lipopolysaccharide (LPS)‐induced interleukin‐6 (IL‐6) and nitric oxide (NO) production in murine microglia

Abstract

Excessive production of proinflammatory cytokines and NO by activated brain microglia play a role in sickness behavior and neurodegenerative disorders. Luteolin, a flavonoid found in high concentrations in celery, green pepper, perilla leaf and seeds, and chamomile, has been shown to reduce proinflammatory molecules in LPS-stimulated macrophages. In the present study, we sought to determine if luteolin also modulates the production of proinflammatory molecules in LPS-stimulated microglial cells. Pretreatment of BV2 murine microglial cells with luteolin inhibited LPS-stimulated IL-6 production at both the gene and protein levels. Luteolin also suppressed LPS-induced NO release in BV2 cells. To determine how luteolin suppressed IL-6 and NO, we investigated phosphorylation of c-Jun-N-terminal kinase (JNK) and found that pretreatment of cells with luteolin attenuated LPS-induced phosphorylation of JNK. In addition, EMSA showed that luteolin inhibited LPS-induced activation of activating protein-1 transcription factor, which mediates IL-6 gene expression. To determine if luteolin might have similar effects in vivo, mice were provided luteolin (0, 1, 2.5, and 5 mg/ml) for 21 days in drinking water and then injected intraperitoneally with LPS (0.333 μg/g B.W.). Luteolin consumption reduced LPS-induced IL-6 in plasma 4 h after injection by nearly 40%. Cytokine expression in brain is currently being assessed. Taken together these data indicate that luteolin can modulate proinflammatory cytokine production in vitro and in vivo. This work was supported by NIH grants AG16710 and MH069148.