Bromelain Inhibits Lipopolysaccharide-Induced Cytokine Production in Human THP-1 Monocytes via the Removal of CD14

Abstract

Bromelain has been reported to have anti-inflammatory and immunomodulatory effects. However, the anti-inflammatory mechanism of bromelain is unclear. Therefore, we investigated the effect of bromelain on cytokine production from lipopolysaccharide (LPS)-stimulated human peripheral blood mononuclear cells (PBMC) and monocytic leukemia THP-1 cells. The result showed that bromelain (50–100 μg/ml) significantly and reversibly reduced tumor necrosis factor (TNF)-α interleukin- (IL)-1β and IL-6 from LPS-induced PBMC and THP-1 cells. This effect was correlated with reduced LPS-induced TNF-α mRNA and NF-κB activity in THP-1 cells. In addition, bromelain dose-dependently inhibited LPS-induced prostaglandin E₂, thromboxane B₂ and COX-2 mRNA but not COX-1 mRNA. Importantly, bromelain degraded TNF-α and IL-1β molecules, reduced the expression of surface marker CD14 but not Toll-like receptor 4 from THP-1 cells. Taken together, the results suggest that the suppression of signaling pathways by bromelain's proteolytic activity may contribute to the anti-inflammatory activity of bromelain.

Keywords:

• Bromelain
• Monocytes
• NF-κB
• COX-2
• TXB2
• MAP Kinases
• CD14