ArticleBritish journal of pharmacology2014
Serine proteases and protease-activated receptor 2 mediate the proinflammatory and algesic actions of diverse stimulants.
Article in British journal of pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
20 citing papers in PubMed, 30 citations in OpenAlex.
- Protease-activated receptors act as a liaison between metabolism and inflammation.Inflammopharmacology · 2026Review
- Proteases and Abdominal Pain-Old Dog, New (Microbial) Tricks.Cellular and molecular gastroenterology and hepatology · 2026Review
- PAR2 regulates proliferation, migration of lung cancer and chemotherapy sensitivity by involving PTEN pathway.Future science OA · 2025Article
- An inhibitor of leukotriene-AProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Review of the Mechanisms of Snake Venom Induced Pain: It's All about Location, Location, Location.International journal of molecular sciences · 2022Review
- Topical Administration of Melatonin-Loaded Extracellular Vesicle-Mimetic Nanovesicles Improves 2,4-Dinitrofluorobenzene-Induced Atopic Dermatitis.Biomolecules · 2021Article
- Immunological Aspects of Skin Aging in Atopic Dermatitis.International journal of molecular sciences · 2021Review
- Ulinastatin Exhibits Antinociception in Rat Models of Acute Somatic and Visceral Pain Through Inhibiting the Local and Central Inflammation.Journal of pain research · 2021Article
- Rhipicephalus microplus serpins interfere with host immune responses by specifically modulating mast cells and lymphocytes.Ticks and tick-borne diseases · 2020Article
- Time-resolved proteomic profile of Amblyomma americanum tick saliva during feeding.PLoS neglected tropical diseases · 2020Article
- Increasing Evidence That Irritable Bowel Syndrome and Functional Gastrointestinal Disorders Have a Microbial Pathogenesis.Frontiers in cellular and infection microbiology · 2020Review
- Protease-Activated Receptor-2 Regulates Neuro-Epidermal Communication in Atopic Dermatitis.Frontiers in immunology · 2020Article
- Amblyomma americanum serpin 27 (AAS27) is a tick salivary anti-inflammatory protein secreted into the host during feeding.PLoS neglected tropical diseases · 2019Article
- Proteinase-activated receptor 2 promotes tumor cell proliferation and metastasis by inducing epithelial-mesenchymal transition and predicts poor prognosis in hepatocellular carcinoma.World journal of gastroenterology · 2018Article
- The putative role of Rhipicephalus microplus salivary serpins in the tick-host relationship.Insect biochemistry and molecular biology · 2016Article
- Global gene expression profiling using heterologous DNA microarrays to analyze alterations in the transcriptome of Mus spretus mice living in a heavily polluted environment.Environmental science and pollution research international · 2016Article
- Molecular and cellular mechanisms that initiate pain and itch.Cellular and molecular life sciences : CMLS · 2015Review
- Mesotrypsin Has Evolved Four Unique Residues to Cleave Trypsin Inhibitors as Substrates.The Journal of biological chemistry · 2015Article
- Conserved Amblyomma americanum tick Serpin19, an inhibitor of blood clotting factors Xa and XIa, trypsin and plasmin, has anti-haemostatic functions.International journal for parasitology · 2015Article
- Proteolytic activation of the human epithelial sodium channel by trypsin IV and trypsin I involves distinct cleavage sites.The Journal of biological chemistry · 2014Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 4 countries.
Funding
Abstract
background and purposeAlthough serine proteases and agonists of protease-activated receptor 2 (PAR2) cause inflammation and pain, the spectrum of proteases that are activated by proinflammatory and algesic stimuli and their contribution to inflammatory pain are uncertain. EXPERIMENTAL APPROACH: Enzymic assays and selective inhibitors were used to characterize protease activity in mice after intraplantar injections of formalin, bradykinin, PAR2 activating peptide (AP) or vehicle. The capacity of these proteases and of recombinant mouse trypsin 4 to cleave fragments of PAR2 and to activate PAR2 in cell lines was determined. Protease inhibitors and par2 (-/-) mice were used to assess the contributions of proteases and PAR2 to pain and inflammation. KEY
resultsIntraplantar injection of formalin, bradykinin or PAR2-AP led to the activation of proteases that were susceptible to the serine protease inhibitor melagatran but resistant to soybean trypsin inhibitor (SBTI). Melagatran inhibited mouse trypsin 4, which degraded SBTI. Proteases generated in inflamed tissues cleaved PAR2-derived peptides. These proteases and trypsin 4 increased [Ca(2+) ]i in PAR2-transfected but not in untransfected cells, and melagatran suppressed this activity. Melagatran or PAR2 deletion suppressed oedema and mechanical hypersensitivity induced by intraplantar formalin, bradykinin and PAR2-AP, but had no effect on capsaicin-induced pain. CONCLUSIONS AND IMPLICATIONS: Diverse proinflammatory and algesic agents activate melagatran-sensitive serine proteases that cause inflammation and pain by a PAR2-mediated mechanism. By inducing self-activating proteases, PAR2 amplifies and sustains inflammation and pain. Serine protease inhibitors can attenuate the inflammatory and algesic effects of diverse stimuli, representing a useful therapeutic strategy.
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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.