3.4 Compound 270 ameliorates the LPS-induced inflammatory
response in bone marrow derived macrophages (BMDMs)
To further clarify that whether 270 possess the direct inhibitory effect
on inflammation in macrophages, we treated primary mouse BMDMs with LPS
alone or combined with 270 and then detected the NF-κB and JNK signaling
pathways, the secretion of inflammatory cytokines and the expression of
pro-inflammatory genes. We found that the LPS-induced activation of
NF-κB and JNK signaling pathways in BMDMs were blocked by the
pretreatment of 270, evidenced by the
reduction
phosphorylation of IKK, NF-κB and JNK, and prevention degradation of
IκB-α in a dose-dependent manner (Figure 4A,B). The release of TNF-α,
IL-6 and MCP 1 from the BMDMs triggered by LPS was also mitigated by 270
administration (Figure 4C). Moreover, 270 remarkably down-regulated the
over-expression of IL-1β, IL-6, MCP 1, Nos2 and COX2 in LPS-stimulated
BMDMs (Figure 4D). In line with the inhibitory ability in RAW 264.7
macrophages. Intriguingly, the repressive effects of 270 on the
LPS-induced inflammatory response were more dramatic in BMDMs than in
RAW 264.7 macrophages. Our investigations revealed that NF-κB inhibitor
270 can against macrophage-mediated inflammatory response, which may
have potential therapeutic effect in inflammation-related diseases.