ArticleThe Journal of biological chemistry2014
Mast cell chymase degrades the alarmins heat shock protein 70, biglycan, HMGB1, and interleukin-33 (IL-33) and limits danger-induced inflammation.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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Who cites it
67 citing papers in PubMed, 120 citations in OpenAlex.
- Advances in targeting IL-1 family cytokines for the treatment of inflammatory diseases.Nature reviews. Rheumatology · 2026Review
- Mast cell proteases and their significance in physiology, pathology, and therapeutic approaches.Pharmacological reviews · 2026Review
- Mast Cells Accumulate in the Stroma of Breast Adenocarcinoma and Secrete Pro-Inflammatory Cytokines and Tumor-Damaging Mediators: Could IL-37 and IL-38 Play an Anti-Tumor Role?International journal of molecular sciences · 2026Review
- Mast cell-derived chymases are essential for the resolution of inflammatory pain in mice.Pain · 2025Article
- HMGB1-dependent signaling in the regulation of mast cell activity during inflammation.Frontiers in immunology · 2025Article
- The deficiency of chymase mast cell protease 4 exacerbates dextran sulfate sodium salt-induced colitis in mice and is associated with altered microbiota and metabolome profiles.Frontiers in cellular and infection microbiology · 2025Article
- Immunological Considerations for the Development of an Effective Herpes Vaccine.Microorganisms · 2024Review
- Basophil-Derived IL-4 and IL-13 Protect Intestinal Barrier Integrity and Control Bacterial Translocation during Malaria.ImmunoHorizons · 2024Article
- Thymic Stromal Lymphopoietin (TSLP) Is Cleaved by Human Mast Cell Tryptase and Chymase.International journal of molecular sciences · 2024Article
- Innate Type-2 Cytokines: From Immune Regulation to Therapeutic Targets.Immune network · 2024Review
- A Deep View of the Biological Property of Interleukin-33 and Its Dysfunction in the Gut.International journal of molecular sciences · 2023Review
- Proteomics investigation of human sera for determination of postoperative indicators of pulmonary cystic echinococcosis.Journal of cardiothoracic surgery · 2023Article
- Article
- Basophil Depletion Alters Host Immunity, Intestinal Permeability, and Mammalian Host-to-Mosquito Transmission in Malaria.ImmunoHorizons · 2022Article
- Targeting the Epithelium-Derived Innate Cytokines: From Bench to Bedside.Immune network · 2022Review
- Mast Cell Chymase/Mcpt4 Suppresses the Host Immune Response toFrontiers in immunology · 2022Article
- Diverse Control Mechanisms of the Interleukin-1 Cytokine Family.Frontiers in cell and developmental biology · 2022Review
- Two Sides of the Coin: Mast Cells as a Key Regulator of Allergy and Acute/Chronic Inflammation.Cells · 2021Review
- Divergent Mast Cell Responses Modulate Antiviral Immunity During Influenza Virus Infection.Frontiers in cellular and infection microbiology · 2021Review
- Steering Mast Cells or Their Mediators as a Prospective Novel Therapeutic Approach for the Treatment of Hematological Malignancies.Frontiers in oncology · 2021Review
7 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
During infection and tissue damage, virulence factors and alarmins are pro-inflammatory and induce activation of various immune cells including macrophages and mast cells (MCs). Activated MCs instantly release preformed inflammatory mediators, including several proteases. The chymase mouse mast cell protease (MCPT)-4 is thought to be pro-inflammatory, whereas human chymase also degrades pro-inflammatory cytokines, suggesting that chymase instead limits inflammation. Here we explored the contribution of MCPT4 and human chymase to the control of danger-induced inflammation. We found that protein extracts from wild type (WT), carboxypeptidase A3-, and MCPT6-deficient mice and MCs and recombinant human chymase efficiently degrade the Trichinella spiralis virulence factor heat shock protein 70 (Hsp70) as well as endogenous Hsp70. MC-(W(sash))-, serglycin-, NDST2-, and MCPT4-deficient extracts lacked this capacity, indicating that chymase is responsible for the degradation. Chymase, but not MC tryptase, also degraded other alarmins, i.e. biglycan, HMGB1, and IL-33, a degradation that was efficiently blocked by the chymase inhibitor chymostatin. IL-7, IL-22, GM-CSF, and CCL2 were resistant to chymase degradation. MCPT4-deficient conditions ex vivo and in vivo showed no reduction in added Hsp70 and only minor reduction of IL-33. Peritoneal challenge with Hsp70 resulted in increased neutrophil recruitment and TNF-α levels in the MCPT4-deficient mice, whereas IL-6 and CCL2 levels were similar to the levels found in WT mice. The rapid and MC chymase-specific degradation of virulence factors and alarmins may depend on the presence of accessible extended recognition cleavage sites in target substrates and suggests a protective and regulatory role of MC chymase during danger-induced inflammation.
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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.