Abstract
Objective- Inflammation is a hallmark of atherosclerosis, which is regulated by numerous cellular and molecular inflammatory mediators, known as cytokines. Visfatin, a novel proinflammatory adipokine, has recently been suggested to play a role in plaque destabilization. Here, we investigated whether visfatin could modulate inflammatory activity in macrophages, key component of plaque formation.
Methods and Results- The THP-1 monocytic cells were differentiated into a macrophage-like phenotype by incubation with phorbol-12-myristate-13-acetate (PMA) in the presence or absence of visfatin. The addition of visfatin increased the production of IL-6, TNF-α, MCP-1, and especially, IL-1β in a dose- and time-dependant manner. Moreover, immunofluorescence or immune blot analysis showed that visfatin induces IκBα phosphorylation and nuclear translocation of the p65 subunit of NF-κB, and the elevated production of inflammatory cytokines was completely abolished by Bay-117082, an inhibitor of NF-κB. Among the mitogen activated protein kinase (MAPK) pathways involved in upstream signaling pathway of NF-κB, visfatin predominantly activated JNK and p38, but not ERK. However, only pretreatment with SP600125, JNK inhibitor, attenuated visfatin-induced effects.
Conclusions- Collectively, these findings indicate that visfatin contribute to inflammatory cytokine production via JNK/NF-κB signaling pathway, consequently leading to the progression of atherosclerosis.
Key word: Visfatin, IL-1β, JNK, NF-κB
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