Coniferaldehyde (CA) exerts anti-inflammatory properties by inducing heme oxygenase-1 (HO-1). To define the regulation mechanism by which CA induces a cytoprotective function and HO-1 expression, the up-stream regulations involved in the activation of nuclear transcription factor-erythroid 2-related factor (Nrf)-2/HO-1 pathway were investigated. CA dramatically increased the Nrf-2 nuclear translocation and HO-1 expression. Lipopolysaccharide (LPS)-induced expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2, and cell death were down-regulated by CA, which were reversed by inhibition of HO-1 activity. Furthermore, CA specifically enhanced the phosphorylation of protein kinase C (PKC) α/β II. Selective inhibition of PKC α/β II using Go6976 or siRNA abolished the CA-induced Nrf-2/HO-1 signaling, and consequently suppressed the cytoprotective activity of CA on the LPS-induced cell death. Together, our results elucidate the regulatory mechanism of PKC α/β II as the upstream molecule of Nrf-2 required for HO-1 expression during CA-induced anti-inflammatory cytoprotective function in LPS stimulated macrophages.
Keywords: Apoptosis; Coniferaldehyde; HO-1; Macrophages; Nrf-2; PKC α/β II.
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