title: Curcumin nanoparticles ameliorate ICAM-1 expression in TNF-α-treated lung epithelial cells through p47 (phox) and MAPKs/AP-1 pathways.
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.
authors.affiliation: Department of Fragrance and Cosmetic Science, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Feng-Lin
authors.initials: FL
authors.lastname: Yen
authors.forename: Ming-Horng
authors.initials: MH
authors.lastname: Tsai
authors.forename: Chuen-Mao
authors.initials: CM
authors.lastname: Yang
authors.forename: Chan-Jung
authors.initials: CJ
authors.lastname: Liang
authors.forename: Chun-Ching
authors.initials: CC
authors.lastname: Lin
authors.forename: Yao-Chang
authors.initials: YC
authors.lastname: Chiang
authors.forename: Hui-Chun
authors.initials: HC
authors.lastname: Lee
authors.forename: Horng-Huey
authors.initials: HH
authors.lastname: Ko
authors.forename: Chiang-Wen
authors.initials: CW
authors.lastname: Lee
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D015153:Blotting, Western; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D003474:Curcumin / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D019255:NADPH Oxidases / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry; D010766:Phosphorylation; D011014:Pneumonia / Q000517:prevention & control; D011205:Povidone / Q000737:chemistry; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D020298:U937 Cells
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; D020928:Mitogen-Activated Protein Kinases; D011205:Povidone; D003474:Curcumin