Differential regulation of c‐Jun N‐terminal kinase and NF‐κB pathway by caffeic acid phenethyl ester in astroglial and monocytic cells

Abstract

Caffeic acid phenethyl ester (CAPE), an active component of propolis extracts, has been known for its specific inhibition of nuclear factor κB (NF‐κB) and subsequent anti‐inflammatory activity. In this study, we report that (i) CAPE exerts its anti‐inflammatory action (inhibition of tumor necrosis factor‐induced expression of intercellular adhesion molecule‐1 and CC chemokine ligand‐2) via NF‐κB inhibition by two distinct molecular mechanisms in a cell‐specific manner: CAPE inhibited downstream pathways of inhibitor κB (IκB) degradation in monocytic cells, while activation of upstream IκB kinase was suppressed by CAPE pre‐treatment in astroglial cells; and (ii) CAPE paradoxically activates the c‐Jun N‐terminal kinase (JNK) pathway, which might be responsible for its pro‐apoptotic action and divergent regulation of proinflammatory mediators such as CXC chemokine ligand‐8.

Neuron Specific Toxicity of Oligomeric Amyloid-β: Role for JUN-Kinase and Oxidative Stress

“…Alternatively, neuronal cultures may have an increased propensity to upregulate pro-apoptotic cascades in response to exposure to oligomeric forms of Aβ compared to astrocytes. For example, in the present study sub-nanomolar concentrations of oligomeric Aβ significantly activated JUN kinase, a signal transduction cascade strongly associated with being pro-apoptotic in numerous cell types [29,30]. Additionally, our present findings suggest that the toxicity of oligomeric Aβ is not mediated by gross perturbations in the plasma membrane, which has been reported previously to mediate toxicity [31,32].…”

Necrotic cells influence migration and invasion of glioblastoma via NF-κB/AP-1-mediated IL-8 regulation

“…In the human pancreatic tumor cell line, NF-κB regulates the expression of c-Fos and the activity of AP-1 in response to ROS and serum condition 30 . In CRT-MG cells, caffeic acid phenethyl ester (CAPE) abrogated TNF-α-induced expression of chemokine (C-C motif) ligand 2 (CCL2) and intercellular adhesion molecule 1 (ICAM-1) via inhibition of NF-κB activation, while increased TNF-α-induced CXCL-8 expression through JNK and AP-1 activation 31 . In another GBM cell line, U251-MG, IL-8 mRNA and protein expression were increased by Ca 2+ -ionophore and phorbol-myristate-acetate via NF-κB and AP-1 signaling, contributing to invasive potential 32 .…”

The effect of caffeic acid phenethyl ester on the functions of human monocyte-derived dendritic cells

“…However, the inhibitory effect of IκBα degradation of CAPE was observed in human middle ear epithelial cells [ 57 ] and gastric epithelial cells [ 58 ]. CAPE inhibited IκB degradation in monocytic cells but not astroglial cells, in which the suppression of activated IKK was shown [ 59 ]. It seemed that in different cells and possible different concentrations of CAPE (10 μM ~100 μM) would result in different inhibitory mechanisms.…”