Curcumin Alleviates oxLDL Induced MMP-9 and EMMPRIN Expression through the Inhibition of NF-κB and MAPK Pathways in Macrophages

Abstract

Rupture of vulnerable atherosclerotic plaques is the leading cause of acute myocardial infarction (AMI) and unstable angina pectoris (UA). However, it still lacks an effective therapy to stabilize the vulnerable atherosclerotic plaques. Numerous reports have shown that upregulation of MMP-9 (matrix metalloproteinase-9) and EMMPRIN (extracellular matrix metalloproteinase inducer) in macrophages is involved in the progression and development of vulnerable plaques. Here we evaluated the impact of curcumin on the expression of MMP-9 and EMMPRIN in macrophages. Macrophages were pretreated with curcumin or specific inhibitors (p38 MAPK inhibitor, NF-κB p65 inhibitor) for 1 h, then cells were cultured with oxLDL for indicated time. Real-time PCR and Western blot analysis were used to evaluate the expression of mRNA and proteins. Translocation of NF-κB p65 was detected by using laser confocal microscopy. Here we showed that curcumin attenuated the MMP-9 and EMMPRIN expression in oxLDL stimulated macrophages. Further studies revealed that curcumin inhibited oxLDL induced NF-κB activation and p38 MAPK phosphorylation. These findings illustrated that curcumin can inhibit the expression of EMMPRIN and MMP-9 in oxLDL stimulated macrophages through down regulation of NF-κB and p38 MAPK signaling pathways, which might be the molecular mechanism for the anti-atherosclerotic effect of curcumin.

Curcumin alleviates macrophage activation and lung inflammation induced by influenza virus infection through inhibiting the NF‐κB signaling pathway

“…These findings indicated that NF‐κB might be a target of curcumin to inhibit the pro‐inflammatory responses of immune cells. Our results are consistent with the anti‐atherosclerotic study of Cao et al., in which they revealed that in oxidized low‐density lipoprotein (oxLDL) stimulated macrophages, curcumin reduced the levels of CD147 and matrix metallopeptidase 9 (MMP‐9) by inhibiting the NF‐κB signaling pathways …”

“…Our results are consistent with the anti-atherosclerotic study of Cao et al, in which they revealed that in oxidized low-density lipoprotein (oxLDL) stimulated macrophages, curcumin reduced the levels of CD147 and matrix metallopeptidase 9 (MMP-9) by inhibiting the NF-κB signaling pathways. 39 In conclusion, we found that IAV infection could result in the inflammatory responses of immune cells, especially macrophages. Our results suggest that curcumin confers protection against IAV-induced acute lung injury by limiting immune cell expanding and downregulating pro-inflammatory cytokine production through inhibiting NF-κB signaling pathway.…”

Metabolomics insights into collagen-induced arthritis in mice and its treatment with wenjinghuoluo prescription

“…In addition, curcumin alleviated oxidative stress in MC3T3-E1 cells by inhibiting P38 and JNK phosphorylation, and 20µM, 1 µM curcumin treatment demonstrated the greatest inhibitory effect respectively, the p-JNK, p-P65 other than p-P38 are the main signaling involved in accordance with the results of osteogenesis. In agreement with our study, curcumin inhibited oxLDLtriggered foam-cell formation through the p38 and JNK pathways [39][40][41]. It has been reported that curcumin prevented diabetic cardiomyopathy by inhibiting the MAPK pathway in diabetic rats [42].…”

Inflammation and dysfunction in human aortic endothelial cells associated with poly‐l‐lactic acid degradation in vitro are alleviated by curcumin

“…Additionally, studies carried out with Cur loaded carriers on cells indicated cytotoxicity (Shelma & Sharma, ). Compared with 30 μM in endothelial cells (Guo et al, ) or 25 μ in macrophages (Cao et al, ) of Cur used in experiments previous in vitro studies, a much lower concentration (5 μM) of Cur was effective and non‐toxic in the present study, which may be attributed to species and cell line differences. In addition, inflammatory effects associated with PLLA were reported in macrophages.…”

“…However, it is PLLA particles instead of extracts that affect macrophages (Wang et al, 2014). Meanwhile, abundant researches indicate the anti-inflammatory effect of curcumin in macrophages (Pan et al, 2013), which is associated with nuclear factor-kappa B (NF-κb) and MAPK Pathways (Cao et al, 2017).…”