ArticleCell death & disease2021
The HIV protease inhibitor Saquinavir attenuates sepsis-induced acute lung injury and promotes M2 macrophage polarization via targeting matrix metalloproteinase-9.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 41 citations in OpenAlex.
- Dabigatran Prevents Lipopolysaccharide-Mediated Apoptosis in Zebrafish Through a Thrombin-Independent Mechanism.Shock (Augusta, Ga.) · 2026Article
- Targeting inflammation and coagulation: MMP-9 deficiency exacerbates sepsis induced acute lung injury through fibrinogen-driven inflammation.Respiratory research · 2026Article
- Targeted silencing of CLYBL with platelet-mimetic siRNA nanoparticles drives itaconate-mediated macrophage reprogramming and protects against sepsis-triggered lung cell death.Cell death discovery · 2026Article
- Network pharmacology-guided optimization of Semen Sojae Praeparatum fermentation for enhanced anti-influenza efficacy.Scientific reports · 2026Article
- DPEP2 suppresses hyperinflammation via metabolic reprogramming of macrophages in sepsis.Nature communications · 2026Article
- Impaired megakaryopoiesis due to aberrant macrophage polarization via BTK/Rap1/NF-κB pathway in sepsis-induced thrombocytopenia.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- V-domain Ig Suppressor of T cell Activation Expression During Hemorrhage or Sepsis-Induced Acute Respiratory Distress Syndrome: Insights From a Mouse Model.The Journal of surgical research · 2025Article
- Mechanisms and Nanomedicine Interventions of Acute Lung Injury Induced by Intestinal Ischemia-Reperfusion: A Mini Review.International journal of nanomedicine · 2025Review
- Construction of a Novel Necroptosis-Related Signature in Rat DRG for Neuropathic Pain.Journal of inflammation research · 2025Article
- Chaihuang Qingfu Pills Protect Against Acute Pancreatitis-Associated Acute Lung Injury Through MMP9-NLRP3-Pyroptosis Pathway.Journal of inflammation research · 2025Article
- Multi-Target Synergy Against Acute Lung Injury: Systems Pharmacology Decoding Dahuang-Huangqin Herb Pair's Therapeutic Mechanism.Journal of inflammation research · 2025Article
- Deleting fibroblast growth factor 2 in macrophages aggravates septic acute lung injury by increasing M1 polarization and inflammatory cytokine secretion.Molecular biomedicine · 2024Article
- Review
- Macrophages in sepsis-induced acute lung injury: exosomal modulation and therapeutic potential.Frontiers in immunology · 2024Review
- Molecular mechanisms of Sepsis attacking the immune system and solid organs.Frontiers in medicine · 2024Review
- Paper-Based Biosensor for the Detection of Sepsis Using MMP-9 Biomarker in FIP Mice Model.Biosensors · 2023Article
- Article
- Exploration of the mechanism by which Huangqi Guizhi Wuwu decoction inhibits Lps-induced inflammation by regulating macrophage polarization based on network pharmacology.BMC complementary medicine and therapies · 2023Article
- The role of macrophages polarization in sepsis-induced acute lung injury.Frontiers in immunology · 2023Review
- Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
Imbalance of macrophage polarization plays an indispensable role in acute lung injury (ALI), which is considered as a promising target. Matrix metalloproteinase-9 (MMP-9) is expressed in the macrophage, and has a pivotal role in secreting inflammatory cytokines. We reported that saquinavir (SQV), a first-generation human immunodeficiency virus-protease inhibitor, restricted exaggerated inflammatory response. However, whether MMP-9 could regulate macrophage polarization and inhibit by SQV is still unknown. We focused on the important role of macrophage polarization in CLP (cecal ligation puncture)-mediated ALI and determined the ability of SQV to maintain M2 over M1 phenotype partially through the inhibition of MMP-9. We also performed a limited clinical study to determine if MMP-9 is a biomarker of sepsis. Lipopolysaccharide (LPS) increased MMP-9 expression and recombinant MMP-9 (rMMP-9) exacerbated LPS-mediated M1 switching. Small interfering RNA to MMP-9 inhibited LPS-mediated M1 phenotype and SQV inhibition of this switching was reversed with rMMP-9, suggesting an important role for MMP-9 in mediating LPS-induced M1 phenotype. MMP-9 messenger RNA levels in peripheral blood mononuclear cells of these 14 patients correlated with their clinical assessment. There was a significant dose-dependent decrease in mortality and ALI after CLP with SQV. SQV significantly inhibited LPS-mediated M1 phenotype and increased M2 phenotype in cultured RAW 264.7 and primary murine bone marrow-derived macrophages as well as lung macrophages from CLP-treated mice. This study supports an important role for MMP-9 in macrophage phenotypic switching and suggests that SQV-mediated inhibition of MMP-9 may be involved in suppressing ALI during systemic sepsis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.