Matrix metalloproteinase-9 (MMP9) has been involved in inflammatory and
pathologic processes of coronary artery lesions (CAL) in
Kawasaki disease (KD).
Intravenous immunoglobulin (
IVIG), a traditional treatment for
Kawasaki disease, could decrease the expressions of MMP9. The purpose of this study was to investigate the protective effect of
IVIG in chemotactic migration of monocyte and the regulation of MMP9 induced by
tumor necrosis factor-α (TNF-α) in U937s. Studies were carried out with real time polymerase chain reaction (RT-PCR), zymographic, Western blotting and immunofluorescence. U937s' migration was enhanced by TNF-α stimulation, while was inhibited by
IVIG pretreatment. MMP9 expression and activity in U937s were also significantly enhanced by TNF-α and inhibited by IVIVG pretreatment. During inflammatory stimulus,
nuclear factor kappa B (NF-κB) and P38 Mitogenactivated
protein kinase (P38 MAPK) pathways play a significant role in regulating MMP9 gene expression. TNF-α induced nuclear translocation of NF-κB and
P38 MAPK activation in U937s were inhibited significantly by
IVIG. Furthermore, we clarified that nuclear NF-κB and
P38 MAPK pathways play pivotal roles in regulating U937s' migration and MMP9 expressions using
PDTC and
SB203580, which were specific inhibitors of NF-κB and
p38 MAPK pathways.
IVIG displays striking
biological effects, notably promoting monocyte migration. These effects involve the NF-κB and p38 pathways, and increased MMP9 activity. It might be a crucial mechanism of
IVIG reducing the occurrence of CAL that
IVIG inhibited monocytes expressing MMP9 and decreased chemotactic migration of monocyte.