Aspirin Inhibits MMP-2 and MMP-9 Expression and Activity Through PPARα/γ and TIMP-1-Mediated Mechanisms in Cultured Mouse Celiac Macrophages

Yao, Yiqin; Xie, Ming; Xue, Jie; Zhang, Keping

doi:10.1007/s10753-009-9125-3

Cited by 36 publications

(27 citation statements)

References 31 publications

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“…A previous study has demonstrated that aspirin, together with its anti-platelet activity, suppressed vascular inflammation and increased the stability of atherosclerotic plaques in murine atherosclerosis, thus exhibiting an anti-atherogenic effect (37). Aspirin can inhibit the expression and release of MMP-2/9 by upregulation of PPARα/γ gene expression, and also inhibit the activity of MMP-2/9 by induction of TIMP1 expression, which may be beneficial for the stabilization of atherosclerotic plaques (38). However, to the best of our knowledge, no studies have reported the potential effects of aspirin on MMP-9 expression in TNF-α-treated RAW264.7 cells.…”

Section: Discussionmentioning

confidence: 99%

Aspirin suppresses TNF‑α‑induced MMP‑9 expression via NF‑κB and MAPK signaling pathways in RAW264.7 cells

Zhang

Huang

et al. 2017

Exp Ther Med

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Abstract. Numerous studies have indicated that the expression of matrix metalloproteinase-9 (MMP-9) contributes to the atherosclerotic plaque hemorrhage and rupture. Aspirin, a non-steroidal anti-inflammation drug, has been known for its anti-platelet effect in the prevention of the vascular complications of atherosclerosis. The present study aimed to investigate the pharmacological effects of aspirin on tumor necrosis factor-α (TNF-α)-induced MMP-9 expression and the underlying molecular mechanisms in murine macrophage RAW264.7 cells. Western blot analysis indicated that the protein level of MMP-9 was reduced by aspirin in a dose-dependent manner. In addition, downregulation of MMP-9 mRNA and activity were detected in aspirin-treated cells using quantitative polymerase chain reaction and a gelatin zymography assay separately. It was also observed that aspirin has a suppressive effect on the activation of nuclear factor (NF)-κB and inhibits the phosphorylation of mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinases 1/2, p38 and c-Jun N-terminal kinase. Furthermore, subsequent to inhibition of the MAPK pathway by specific inhibitors (PD98059, SB203580 and SP600125), the expression of MMP-9 was reduced, indicating that the inhibitory effect of aspirin on MMP-9 in TNF-α-treated RAW264.7 cells may be, at least in part, through suppression of NF-κB activation and the MAPK pathway. These findings support the notion that aspirin has therapeutic potential application in the prevention and treatment of atherosclerosis disease.

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Section: Discussionmentioning

confidence: 99%

Aspirin suppresses TNF‑α‑induced MMP‑9 expression via NF‑κB and MAPK signaling pathways in RAW264.7 cells

Zhang

Huang

et al. 2017

Exp Ther Med

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“…Indeed, some anti-inflammatory drugs also alter MMP-9 and TIMP-1 expression and function. For example, aspirin was shown to inhibit MMP-9 activity by inducing the expression of TIMP-1 in cultured mouse celiac macrophages (Yiqin et al 2009). Thus, the inhibition of MMP-9 by LXA 4 ME may be caused by enhancing the expression of TIMP-1.…”

Section: Discussionmentioning

confidence: 99%

A Lipoxin A4 Analog Ameliorates Blood–Brain Barrier Dysfunction and Reduces MMP-9 Expression in a Rat Model of Focal Cerebral Ischemia–Reperfusion Injury

Wang

Guo

et al. 2011

J Mol Neurosci

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LXA(4) methyl ester (LXA(4)ME), a lipoxin A(4) analog, reduces ischemic insult in the rat models of transient or permanent cerebral ischemic injury. We investigated whether LXA(4)ME could ameliorate blood-brain barrier (BBB) dysfunction after stroke by reducing matrix metalloproteinase (MMP)-9 expression. Adult male rats were subjected to 2-h middle cerebral artery occlusion (MCAO) followed by 24-h reperfusion. Brain infarctions were detected by triphenyltetrazolium chloride (TTC) staining. BBB dysfunction was determined by examining brain edema and Evans Blue extravasation. Temporal expression of MMP-9 was determined by zymography and Western blot. The presence of tissue inhibitors of metalloproteinase-1 (TIMP-1) was also determined by Western blot in tissue protein sample. Brain edema and Evans Blue leakage were significantly reduced after stroke in the LXA(4)ME group and were associated with reduced brain infarct volumes. MMP-9 activity and expression were inhibited by LXA(4)ME after stroke. In addition, LXA(4)ME significantly increased TIMP-1 protein levels. Our results indicate that LXA(4)ME reduces brain injury by improving BBB function in a rat model of MCAO, and that a relationship exists between BBB permeability and MMP-9 expression following ischemic insult. Furthermore, these results suggest that LXA(4)ME-mediated reduction of MMP-9 following stroke are attributed to increased TIMP-1 expression.

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“…During inflammatory response, MMPs produced by macrophages also play important roles and contribute to infiltration of leukocytes into tissues[7, 8, 21]. Therefore, we investigated the effects of BER on LPS-induced MMP-2 and MMP-9 expression, as well as secretion by macrophages.…”

Section: Resultsmentioning

confidence: 99%

“…In order to comprehensively clarify the anti-inflammatory activity of BER, we determined the effects of BER on the expression of COX2 and PGE2 production, which results show that BER also intensively inhibits the expression of COX2 and PGE2 production by macrophages. In addition, macrophages can release MMPs to facilitate infiltration of immune cells during inflammatory response[7, 8]. So we also evaluated the effects of BER on the expression and secretion of MMP2 and MMP-9.…”

Section: Discussionmentioning

confidence: 99%

Berbamine Exerts Anti-Inflammatory Effects via Inhibition of NF-κB and MAPK Signaling Pathways

Jia

Wang

et al. 2017

Cell Physiol Biochem

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Background/Aims: This study aimed to investigate the anti-inflammatory activity of Berbamine (BER), a bisbenzylisoquinoline alkaloid extracted from Berberis amurensis (Xiao Bo An), and the underlying mechanisms. Methods: Macrophages and neutrophils were treated with BER in vitro and stimulated with LPS and fMLP. The effects of BER on the expression of pro-inflammatory mediators in macrophages were evaluated with quantitative RT-PCR and ELISA. The effects of BER on the activation and superoxide release of neutrophils were determined with flow cytometry and WST-1 reduction test. The inhibitory effects of BER on the activation of signaling pathways related to inflammatory response in macrophages were evaluated by western blot analysis. In addition, a mouse peritonitis model was made by peritoneal injection of thioglycollate medium and anti-inflammatory effects of BER were investigated in vivo by quantitative analysis of pro-inflammatory factor production and leukocyte exudation. Results: BER significantly inhibited inflammatory factor expression by LPS-stimulated macrophages and suppressed activation and superoxide release of fMLP-stimulated neutrophils. In the mouse peritonitis model, BER significantly inhibited the activation of macrophages and exudation of neutrophils. According to analysis, BER significantly suppressed phosphorylation of NF-κB and MAPK (JNK and ERK1/2) signaling pathways in LPS-stimulated macrophages. Conclusions: Collectively, data from this study suggest that BER has anti-inflammatory potential, which is effected via inhibition of NF-κB and MAPK signaling pathways, and thus holds promise for treatment of inflammatory disease.

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Aspirin Inhibits MMP-2 and MMP-9 Expression and Activity Through PPARα/γ and TIMP-1-Mediated Mechanisms in Cultured Mouse Celiac Macrophages

Cited by 36 publications

References 31 publications

Aspirin suppresses TNF‑α‑induced MMP‑9 expression via NF‑κB and MAPK signaling pathways in RAW264.7 cells

Aspirin suppresses TNF‑α‑induced MMP‑9 expression via NF‑κB and MAPK signaling pathways in RAW264.7 cells

A Lipoxin A4 Analog Ameliorates Blood–Brain Barrier Dysfunction and Reduces MMP-9 Expression in a Rat Model of Focal Cerebral Ischemia–Reperfusion Injury

Berbamine Exerts Anti-Inflammatory Effects via Inhibition of NF-κB and MAPK Signaling Pathways

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