Trypsin and mast cell tryptase cleave proteinase-activated receptor 2 and, by unknown mechanisms, induce widespread inflammation. We found that a large proportion of primary spinal afferent neurons, which express proteinase-activated receptor 2, also contain the proinflammatory neuropeptides calcitonin gene-related peptide and substance P. Trypsin and tryptase directly signal to neurons to stimulate release of these neuropeptides, which mediate inflammatory edema induced by agonists of proteinase-activated receptor 2. This new mechanism of protease-induced neurogenic inflammation may contribute to the proinflammatory effects of mast cells in human disease. Thus, tryptase inhibitors and antagonists of proteinase-activated receptor 2 may be useful anti-inflammatory agents.
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http://dx.doi.org/10.1038/72247 | DOI Listing |
BMJ Open Respir Res
January 2025
Murdoch Children's Research Institute, Parkville, Victoria, Australia.
Background: The most common cause of death in those with cystic fibrosis (CF) is respiratory failure due to bronchiectasis resulting from repeated cycles of respiratory infection and inflammation. Protease-activated receptor 1 (PAR1) is a cell surface receptor activated by serine proteases including neutrophil elastase, which is recognised as a potent modulator of inflammation. While PAR1 is known to play an important role in regulating inflammation, nothing is known about any potential role of this receptor in CF pathogenesis.
View Article and Find Full Text PDFAm J Transl Res
December 2024
Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University Tianjin 300070, China.
Proteinase-activated receptor-2 (PAR2) is closely linked to tumor malignancy, but its biological role in cancer remains underexplored. In this study, we assessed PAR2 expression in lung adenocarcinoma (LUAD) and normal lung tissues, analyzed associations between clinicopathological features and survival rates, and confirmed that PAR2 promotes apoptosis resistance and reduces cisplatin-induced cytotoxicity in lung cancer cells. Using TCGA datasets, western blotting, qPCR, and immunohistochemistry (IHC), we observed a significant increase in PAR2 levels in LUAD samples compared to normal tissues (P<0.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
The Azrieli Faculty of Medicine, Bar-Ilan University, Safed 1311502, Israel.
Autoimmune diseases are complex conditions characterized by immune-mediated tissue damage and chronic inflammation. Protease-activated receptor 2 (Par2) has been implicated in these diseases, exhibiting dual roles that complicate its therapeutic potential. This review examines the perplexing functions of Par2, which promotes inflammation through immune cell activation while facilitating tissue healing in damaged organs.
View Article and Find Full Text PDFAdv Sci (Weinh)
December 2024
Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
Parkinson's disease (PD) is characterized by the deposition of misfolded α-synuclein (α-syn) in the brain. Converging evidence indicates that the intracellular transmission and subsequent templated amplification of α-syn are involved in the onset and progression of PD. However, the molecular mechanisms underlying the cell-to-cell transmission of pathological α-syn remain poorly understood.
View Article and Find Full Text PDFBiochem Biophys Res Commun
January 2025
Department of Biotechnology, Bharathiar University, Coimbatore, India. Electronic address:
Tissue factor (TF) and protease-activated receptor 2 (PAR2) have been associated with the progression of cancer, while integrins are essential for the adhesion and migration of cancer cells. This study aimed to explore the cross-talk between the TF:FVIIa complex, PAR2 signaling, and the expression of integrin α1 in cervical cancer cells. Utilizing data from The Cancer Genome Atlas (TCGA), the research examined the relationship between the TF and PAR2 genes and the integrin α1 gene (ITGA1) in reproductive cancers, revealing a positive correlation between integrin α1 expression and both TF and PAR2 genes.
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