Abstract
Upregulation of intercellular adhesion molecule-1 (ICAM-1) involves adhesions between both circulating and resident leukocytes and the human lung epithelial cells during lung inflammatory reactions. We have previously demonstrated that curcumin-loaded polyvinylpyrrolidone nanoparticles (CURN) improve the anti-inflammatory and anti-oxidative properties of curcumin in hepatocytes. In this study, we focused on the effects of CURN on the expression of ICAM-1 in TNF-α-treated lung epithelial cells and compared these to the effects of curcumin water preparation (CURH). TNF-αinduced ICAM-1 expression, ROS production, and cell-cell adhesion were significantly attenuated by the pretreatment with antioxidants (DPI, APO, or NAC) and CURN, but not by CURH, as revealed by western blot analysis, RT-PCR, promoter assay, and ROS detection and adhesion assay. In addition, treatment of TNF-α-treated cells with CURN and antioxidants also resulted in an inhibition of activation of p47 phox and phosphorylation of MAPKs, as compared to that using CURH. Our findings also suggest that phosphorylation of MAPKs may eventually lead to the activation of transcription factors. We also observed that the effects of TNF-α treatment for 30 min, which includes a significant increase in the binding activity of AP-1 and phosphorylation of c-jun and c-fos genes, were reduced by CURN treatment. In vivo studies have revealed that CURN improved the anti-inflammation activities of CURH in the lung epithelial cells of TNF-α-treated mice. Our results indicate that curcumin-loaded polyvinylpyrrolidone nanoparticles may potentially serve as an anti-inflammatory drug for the treatment of respiratory diseases.
Highlights
Lung inflammation is a critical event in the pathogenesis of various diseases, including asthma, chronic obstructive pulmonary disease (COPD), severe acute respiratory syndrome (SARS), and cancer [1,2]
These results suggested that pretreatment with curcumin-loaded polyvinylpyrrolidone nanoparticles (CURN) inhibits TNF-a-induced lung inflammatory responses, which may be regulated by Intercellular adhesion molecule-1 (ICAM-1) inhibition
Pretreatment with CURN, NAC and diphenyleneiodonium chloride (DPI) resulted in a significant decrease in TNF-ainduced MAPKs phosphorylation, whereas no similar effects were observed with that using CURH. These results suggest that CURN imparts stronger inhibitory effects than CURH on TNF-ainduced MAPKs phosphorylation, which resulted from the inhibition of the NOX2/ROS-dependent pathway in A549 cells
Summary
Lung inflammation is a critical event in the pathogenesis of various diseases, including asthma, chronic obstructive pulmonary disease (COPD), severe acute respiratory syndrome (SARS), and cancer [1,2]. Upregulation of ICAM-1 by cytokines has been shown to be regulated by the phosphorylation of three MAPKs, p38, JNK1/2, and Erk1/2, as well as transcription factors such as nuclear factor kB (NF-kB) and activator protein 1 (AP-1) in lung epithelial cells [5,6]. Increasing evidence have shown that NADPH oxidase (NOX)-derived ROS generation can modify signaling through the oxidation of reactive cysteines within certain cell signaling molecules, especially MAPKs or transcription factors such as NF-kB and AP-1 [7,8]. Elevated levels of ROS have been shown to activate signal transduction cascades and to drive the expression of adhesion molecules such as ICAM-1 and VCAM-1 in endothelial cells, epithelial cells, fibroblasts, and astrocytes [13,14]. Blockade of ROS production may be selectively targeted to reduce neutrophil adhesion through adhesion molecule suppression and attenuation of the inflammatory responses in lung diseases
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