Curcumin Suppresses Lipopolysaccharide-Induced Cyclooxygenase-2 Expression by Inhibiting Activator Protein 1 and Nuclear Factor κB Bindings in BV2 Microglial Cells

Abstract

Inflammation is a significant component of chronic neurodegenerative diseases. Cyclooxygenase-2 (COX-2) is expressed in activated microglial cells and appears to be an important source of prostaglandins during inflammatory conditions. To investigate the effect of curcumin on COX-2 gene expression in microglial cells, we treated lipopolysaccharide (LPS)-challenged BV2 microglial cells with various concentrations of curcumin. Curcumin significantly inhibited LPS-mediated induction of COX-2 expression in both mRNA and protein levels in a concentration-dependent manner. COX-2 enzyme activity was also inhibited in accordance with mRNA and protein levels. Furthermore, curcumin markedly inhibited LPS-induced nuclear factor kB (NF-kB) and activator protein 1 (AP-1) DNA bindings. These data suggest that curcumin suppresses LPS-induced COX-2 gene expression by inhibiting NF-k B and AP-1 DNA bindings in BV2 microglial cells.

Curcumin inhibits the expression of COX-2 in UVB-irradiated human keratinocytes (HaCaT) by inhibiting activation of AP-1: p38 MAP kinase and JNK as potential upstream targets

“…Accumulating evidences suggest that curcumin inhibits the expression of COX-2 in several experimental models (Zhang et al, 1999;Chun et al, 2003;Surh, 2003;Kang et al, 2004). Consistent with these, through the present study, we have demonstrated that curcumin also effectively inhibits the expressions of COX-2 mRNA and protein induced by UVB irradiation in a human keratinocyte cell line HaCaT, which seems to be, to our knowledge, the first report.…”

“…Curcumin is known to exert its anti-inflammatory action in various cell lines through inhibition of COX-2 expression (Chun et al, 2003;Kang et al, 2004). Thus, it is important to develop an efficient strategy using curcumin to down-regulate the expression of COX-2 in UVB-irradiated skin (Wolf et al, 2003).…”

“…Consistent with these, through the present study, we have demonstrated that curcumin also effectively inhibits the expressions of COX-2 mRNA and protein induced by UVB irradiation in a human keratinocyte cell line HaCaT, which seems to be, to our knowledge, the first report. Accordingly, the expression of COX-2 has been shown to be affected by various intracellular signaling proteins such as p38 MAPK and JNK (Goel et al, 2001;Surh et al, 2001;Liu et al, 2003;Lin et al, 2004;Kang et al, 2004). Interestingly, it has been recently shown that UVB induces the expression of COX-2 by activation of p38 MAPK in HaCaT cells (Chen et al, 2001) or by activations of p38 MAPK and JNK in artificial epidermis (Mahns et al, 2004).…”

“…Recently, it has been reported that curcumin-treated cells show the decreased expressions of COX-2 in various cell lines by inhibition of MAPKs signaling pathways (Chun et al, 2003;Hong et al, 2004;Kang et al, 2004). Currently, it is unknown whether curcumin modulates the expression of COX-2 in UVB-irradiated HaCaT cells.…”

Anti-inflammatory effects of lipoic acid through inhibition of GSK-3β in lipopolysaccharide-induced BV-2 microglial cells

“…Microglial cells are important players in immune and inflammatory responses in the CNS (Nam et al 2010), and their activation is implicated in several chronic neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD) and brain ischemia (Kang et al 2004). Activated microglial cells promote neuronal injury via the production of pro-inflammatory molecules such as the cytokines, tumor necrosis factor (TNF) α and interleukin (IL)-1β, and other cytotoxic molecules, such as reactive oxygen species (ROS) (Dheen et al 2007).…”