Chlorophyll-related compounds inhibit cell adhesion and inflammation in human aortic cells.
The objectives of this study were to investigate the effects of chlorophyll-related compounds (CRCs) and chlorophyll (Chl) a+b on inflammation in human aortic endothelial cells. Adhesion molecule expression and interleukin (IL)-8, nuclear factor (NF)-κB p65 protein, and NF-κB and activator protein (AP)-1 DNA binding were assessed. The effects of CRCs on inflammatory signaling pathways of signal transducers and activators of transcription 3 (STAT3) and mothers against decapentaplegic homolog 4, respectively induced by IL-6 and transforming growth factor (TGF)-β, in human aortic smooth muscle cells cultured in vitro were also investigated. HAECs were pretreated with 10 μM of CRCs, Chl a+b, and aspirin (Asp) for 18 h followed by tumor necrosis factor (TNF)-α (2 ng/mL) for 6 h, and U937 cell adhesion was determined. TNF-α-induced monocyte-endothelial cell adhesion was significantly inhibited by CRCs. Moreover, CRCs and Chl a+b significantly attenuated vascular cell adhesion molecule-1, intercellular adhesion molecule-1, and IL-8 expressions. Treatments also significantly decreased in NF-κB expression, DNA binding, and AP-1 DNA binding by CRCs and Asp. Thus, CRCs exert anti-inflammatory effects through modulation of NF-κB and AP-1 signaling. Ten micromoles of CRCs and Asp upregulated the expression of mothers against decapentaplegic homolog 4 (Drosophila) (SMAD4) in the TGF-β receptor signaling pathway, and SMAD3/4 transcription activity was also increased. Ten micromoles of CRCs were able to potently inhibit STAT3-binding activity by repressing IL-6-induced STAT3 expression. Our results provide a potential mechanism that explains the anti-inflammatory activities of these CRCs.
1 Graduate Institute of Biotechnology, Chinese Culture University , Taipei, Taiwan .
Kuan-Hung
KH
Lin
Ching-Yun
CY
Hsu
Ya-Ping
YP
Huang
Jun-You
JY
Lai
Wen-Bin
WB
Hsieh
Meng-Yuan
MY
Huang
Chi-Ming
CM
Yang
Pi-Yu
PY
Chao
D001011:Aorta / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D050197:Atherosclerosis / Q000188:drug therapy / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology; D002448:Cell Adhesion / Q000187:drug effects*; D002734:Chlorophyll / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000276:immunology; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology; D016209:Interleukin-8 / Q000235:genetics / Q000276:immunology; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology; D020298:U937 Cells
D015850:Interleukin-6; D016209:Interleukin-8; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D002734:Chlorophyll