Doxycycline alleviates paraquat-induced acute lung injury by inhibiting neutrophil-derived matrix metalloproteinase 9

Zhang, Feng; Hu, Liang; Wu, Yuxuan; Fan, Lu; Li, Wentao; Wang, Jun; Sun, Huiling; Zhang, Jinsong

doi:10.1016/j.intimp.2019.04.015

Cited by 37 publications

(27 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition to TIMPs, synthetic inhibitors against MMPs have also been shown to be effective, and of these, doxycycline has been approved by the American Food and Drug Administration for clinical practice [ 113 , 114 ]. Doxycycline inhibits the expression and activity of MMP-9 [ 115 , 116 ], and doxycycline treatment can significantly inhibit atherosclerosis development [ 117 ]. Doxycycline can also reduce the neointimal thickness and has a protective effect on left ventricular dilation [ 118 ].…”

Section: Pharmacotherapy Targeting Mmp-9 In Atherosclerosismentioning

confidence: 99%

The Role of Matrix Metalloproteinase-9 in Atherosclerotic Plaque Instability

Feng

et al. 2020

Mediators of Inflammation

View full text Add to dashboard Cite

Matrix metalloproteinase-9 (MMP-9) belongs to the MMP family and has been widely investigated. Excessive MMP-9 expression can enhance extracellular matrix degradation and promote plaque instability. Studies have demonstrated that MMP-9 levels are higher in vulnerable plaques than in stable plaques. Additionally, several human studies have demonstrated that MMP-9 may be a predictor of atherosclerotic plaque instability and a risk factor for future adverse cardiovascular and cerebrovascular events. MMP-9 deficiency or blocking MMP-9 expression can inhibit plaque inflammation and prevent atherosclerotic plaque instability. All of these results suggest that MMP-9 may be a useful predictive biomarker for vulnerable atherosclerotic plaques, as well as a therapeutic target for preventing atherosclerotic plaque instability. In this review, we describe the structure, function, and regulation of MMP-9. We also discuss the role of MMP-9 in predicting and preventing atherosclerotic plaque instability.

show abstract

Section: Pharmacotherapy Targeting Mmp-9 In Atherosclerosismentioning

confidence: 99%

The Role of Matrix Metalloproteinase-9 in Atherosclerotic Plaque Instability

Feng

et al. 2020

Mediators of Inflammation

View full text Add to dashboard Cite

show abstract

“…I/R-induced lung injury occurring following lung transplantation is characterized by lung inflammation. 23 Intravenously administered syngeneic iPSCs exert therapeutic effects on multiple diseases, and our previous study reported the beneficial effects of iPSCs on paraquat-induced lung injury. 10 However, the mechanisms underlying the protective effects of iPSCs require further investigation.…”

Section: Discussionmentioning

confidence: 99%

Induced Pluripotent Stem Cells Attenuate Acute Lung Injury Induced by Ischemia Reperfusion via Suppressing the High Mobility Group Box-1

Wang

et al. 2020

Dose-Response

View full text Add to dashboard Cite

Pulmonary endothelial cell injury is a hallmark of acute lung injury. High-mobility group box 1 (HMGB1) can modulate the inflammatory response via endothelial cell activation and release of inflammatory molecules. Thus, we tested whether induced pluripotent stem cells (iPSCs) can alleviate ischemia/reperfusion (I/R) induced lung injury, and, if so, whether HMGB1 mediates the effect in a male C57BL/6 mouse model. Intravenously injected iPSCs into mice 2 h after I/R showed a significant attenuation of lung injury (assessed by lung mechanics, edema, and histology) 24 h after reperfusion (compared with controls), along with decreases in HMGB1, phosphorylated nuclear factor-κB, inflammatory cytokines [interleukin (IL)1β, IL6 and tumor necrosis factor-α], and the activation of endothelial cells. Furthermore, these effects of iPSCs can be mimicked by blocking HMGB1 with an inhibitor in vivo and in vitro. We conclude that iPSCs can be a potential therapy for I/R-induced lung injury. These cells may exert therapeutic effects through blocking HMGB1 and inflammatory cytokines.

show abstract

“…Referring to our previous study [ 24 ], male C57BL/6J mice (8–9 wk. old) were administered PQ (Sigma-Aldrich, MO, USA) at a single dose of 0.02 mg per mouse (PQ diluted in 50 μ l of sterile saline buffer) via intratracheal aerosolization (Model IAIC microsprayer, High Pressure Syringe Model FMJ-250, Penn-Century, PA, USA).…”

Section: Methodsmentioning

confidence: 99%

The MUC5B Mucin Is Involved in Paraquat-Induced Lung Inflammation

Sun

Jiang

Song

et al. 2020

Oxidative Medicine and Cellular Longevity

Self Cite

View full text Add to dashboard Cite

Objective. Paraquat (PQ), a widely used toxic herbicide, induces lung inflammation through mechanisms that remain incompletely understood. In a previous study, we found that the plasma MUC5B mucin level was implicated in PQ poisoning in patients. Here, we hypothesize that MUC5B is a critical mediator in PQ-induced cell inflammation. Methods. A mouse model of PQ-induced lung injury was used to examine the MUC5B expression level. A549 cells (alveolar epithelial cells line) were exposed to PQ in dose-dependent and time-dependent manners. Cell viability was detected by CCK-8 assays. The expression levels of MUC5B were examined by dot blot enzyme-linked immunosorbent assay (ELISA) and RT-qPCR. Western blotting was used to detect the levels of proteins in the MAPK and NF-κB pathways. Inflammatory factors in the cell culture medium were measured by ELISA. NF-κB and MAPK pathway inhibitors and MUC5B siRNA (siMUC5B) were used to determine the function of MUC5B. Finally, N-acetyl-cysteine (NAC) was added and its regulatory effect on the MAPK-NF-κB-MUC5B pathway was examined in PQ-induced cell inflammation. Results. MUC5B was significantly upregulated accompanying the increases in TNF-α and IL-6 secretion following PQ treatment in mouse and also in A549 cells after treatment with 50 μM PQ at 24 hours. Furthermore, MAPK and NF-κB pathway inhibitors could dramatically decrease the expression of MUC5B and the secretion of TNF-α and IL-6. Importantly, siMUC5B could significantly attenuate the secretion of TNF-α and IL-6 induced by PQ. As expected, the addition of NAC efficiently suppresses the TNF-α and IL-6 secretion stimulated from PQ and also downregulated ERK, JNK, and p65 phosphorylation (ERK/JNK MAPK and NF-κB pathways) as well as MUC5B expression. Conclusion. Our findings suggest that MUC5B participates in the process of PQ-induced cell inflammation and is downstream of the NF-κB and MAPK pathways. NAC can attenuate PQ-induced cell inflammation at least in part by suppressing the MAPK-NF-κB-MUC5B pathway. These results nominate MUC5B as a new biomarker and therapeutic target for PQ-induced lung inflammation.

show abstract

Doxycycline alleviates paraquat-induced acute lung injury by inhibiting neutrophil-derived matrix metalloproteinase 9

Cited by 37 publications

References 43 publications

The Role of Matrix Metalloproteinase-9 in Atherosclerotic Plaque Instability

The Role of Matrix Metalloproteinase-9 in Atherosclerotic Plaque Instability

Induced Pluripotent Stem Cells Attenuate Acute Lung Injury Induced by Ischemia Reperfusion via Suppressing the High Mobility Group Box-1

The MUC5B Mucin Is Involved in Paraquat-Induced Lung Inflammation

Contact Info

Product

Resources

About