L-cystathionine inhibits oxidized low density lipoprotein-induced THP-1-derived
macrophage inflammatory cytokine monocyte chemoattractant protein-1 generation
via the NF-?B pathway
#MMPMID26020416
Zhu M
; Du J
; Liu AD
; Holmberg L
; Chen SY
; Bu D
; Tang C
; Jin H
Sci Rep
2015[May]; 5
(?): 10453
PMID26020416
show ga
This study aimed to explore whether and how L-cystathionine had any regulatory
effect on the inflammatory response in THP-1-derived macrophages cultured in
vitro under oxidized low-density lipoprotein (ox-LDL) stimulation. The human
monocyte line THP-1 cell was cultured in vitro and differentiated into
macrophages after 24?hours of PMA induction. Macrophages were pretreated with
L-cystathionine and then treated with ox-LDL. The results showed that compared
with the controls, ox-LDL stimulation significantly upregulated the expression of
THP-1-derived macrophage MCP-1 by enhancing NF-?B p65 phosphorylation, nuclear
translocation and DNA binding with the MCP-1 promoter. Compared with the ox-LDL
group, 0.3?mmol/L and 1.0?mmol/L L-cystathionine significantly inhibited the
expression of THP-1-derived macrophage MCP-1. Mechanistically, 0.3?mmol/L and
1.0?mmol/L L-cystathionine suppressed phosphorylation and nuclear translocation
of the NF-?B p65 protein, as well as the DNA binding activity and DNA binding
level of NF-?B with the MCP-1 promoter, which resulted in a reduced THP-1-derived
macrophage MCP-1 generation. This study suggests that L-cystathionine could
inhibit the expression of MCP-1 in THP-1-derived macrophages induced by ox-LDL
via inhibition of NF-?B p65 phosphorylation, nuclear translocation, and binding
of the MCP-1 promoter sequence after entry into the nucleus.