ArticleJournal of immunology (Baltimore, Md. : 1950)2014
IL-6-mediated induction of matrix metalloproteinase-9 is modulated by JAK-dependent IL-10 expression in macrophages.
Article in Journal of immunology (Baltimore, Md. : 1950), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
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Who cites it
75 citing papers in PubMed, 134 citations in OpenAlex.
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- A preclinical model to investigate the role of surgically-induced inflammation in tumor responses to intraoperative photodynamic therapy.Lasers in surgery and medicine · 2018Trial
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- The Blockade of Delta-Like Ligand 1 Inhibits Atherosclerotic Lesion Formation and Attenuates Plaque Vulnerability.Journal of atherosclerosis and thrombosis · 2026Article
- Tear cytokine profiles between children with allergic conjunctivitis at varying eye rubbing frequencies and keratoconus: A cross-sectional study.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2026Article
- Review
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- MMP-9 dysregulation and chronic inflammation in polycystic ovary syndrome: linking ovulatory dysfunction to diagnostic implications.Journal of ovarian research · 2025Article
- Rituximab for antibody-negative combined central and peripheral demyelination presenting with acute respiratory failure: a case report and literature review.Frontiers in immunology · 2025Review
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- Neutrophil Biomarkers Can Predict Cardiotoxicity of Anthracyclines in Breast Cancer.International journal of molecular sciences · 2024Article
- Activated THP-1 Macrophage-Derived Factors Increase the Cytokine, Fractalkine, and EGF Secretions, the Invasion-Related MMP Production, and Antioxidant Activity of HEC-1A Endometrium Cells.International journal of molecular sciences · 2024Article
- STAT3 Deficiency Alters the Macrophage Activation Pattern and Enhances Matrix Metalloproteinase 9 Expression during Staphylococcal Pneumonia.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Interleukin-6 in Traumatic Brain Injury: A Janus-Faced Player in Damage and Repair.Journal of neurotrauma · 2023Review
- Experimental venous thrombus resolution is driven by IL-6 mediated monocyte actions.Scientific reports · 2023Article
- Evaluation of MMP-9, IL-6, TNF-α levels and peripheral blood mononuclear cells genes expression of MMP-9 and TIMP-1 in Iranian patients with coronary artery disease.Journal of cardiovascular and thoracic research · 2023Article
- Mare stromal endometrial cells differentially modulate inflammation depending on oestrus cycle status: anFrontiers in veterinary science · 2023Article
- Cytokine response and damages in the lungs of aging Syrian hamsters on a high-fat diet infected with the SARS-CoV-2 virus.Frontiers in immunology · 2023Article
15 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The mechanisms by which IL-6 contributes to the pathogenesis of chronic inflammatory diseases and cancer are not fully understood. We previously reported that cyclooxygenase-2 (Cox-2)-dependent PGE2 synthesis regulates macrophage matrix metalloproteinase (MMP)-9 expression, an endopeptidase that participates in diverse pathologic processes. In these studies, we determined whether IL-6 regulates the Cox-2→PGE2→MMP-9 pathway in murine macrophages. IL-6 coinduced Cox-2 and microsomal PGE synthase-1, and inhibited the expression of 15-hydroxyprostaglandin dehydrogenase, leading to increased levels of PGE2. In addition, IL-6 induced MMP-9 expression, suggesting that the observed proteinase expression was regulated by the synthesis of PGE2. However, inhibition of PGE2 synthesis partially suppressed IL-6-mediated induction of MMP-9. In the canonical model of IL-6-induced signaling, JAK activation triggers STAT and MAPK(erk1/2)-signaling pathways. Therefore, the ability of structurally diverse JAK inhibitors to block IL-6-induced MMP-9 expression was examined. Inhibition of JAK blocked IL-6-induced phosphorylation of STAT3, but failed to block the phosphorylation of MAPK(erk1/2), and unexpectedly enhanced MMP-9 expression. In contrast, MEK-1 inhibition blocked IL-6-induced phosphorylation of MAPK(erk1/2) and MMP-9 expression without affecting the phosphorylation of STAT3. Thus, IL-6-induced MMP-9 expression is dependent on the activation of MAPK(erk1/2) and is restrained by a JAK-dependent gene product. Using pharmacologic and genetic approaches, we identified JAK-dependent induction of IL-10 as a potent feedback mechanism controlling IL-6-induced MMP-9 expression. Together, these data reveal that IL-6 induces MMP-9 expression in macrophages via Cox-2-dependent and -independent mechanisms, and identifies a potential mechanism linking IL-6 to the pathogenesis of chronic inflammatory diseases and cancer.
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Registered trials
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.