ArticleThe Journal of biological chemistry2012
Disruption of proprotein convertase 1/3 (PC1/3) expression in mice causes innate immune defects and uncontrolled cytokine secretion.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 38 citations in OpenAlex.
- Neuroendocrinology and the Genetics of Obesity.Endocrinology · 2025Review
- Inhibition of furin in CAR macrophages directs them toward a proinflammatory phenotype and enhances their antitumor activities.Cell death & disease · 2024Article
- Ablation of PC1/3 in POMC-Expressing Tissues but Not in Immune Cells Induces Sepsis Hypersensitivity.Journal of the Endocrine Society · 2024Article
- Loss-of-function mutation in Pcsk1 increases serum APOA1 level and LCAT activity in mice.Laboratory animal research · 2022Article
- Therapeutic anti-glioma effect of the combined action of PCSK inhibitor with the anti-tumoral factors secreted by Poly (I:C)-stimulated macrophages.Cancer gene therapy · 2022Article
- Mouse Models of Human Proprotein Convertase Insufficiency.Endocrine reviews · 2021Review
- The Role of Proprotein Convertases in the Regulation of the Function of Immune Cells in the Oncoimmune Response.Frontiers in immunology · 2021Review
- Epigenetic Studies Revealed a Ghost Proteome in PC1/3 KD Macrophages under Antitumoral Resistance Induced by IL-10.ACS omega · 2020Article
- The Role of a Proprotein Convertase Inhibitor in Reactivation of Tumor-Associated Macrophages and Inhibition of Glioma Growth.Molecular therapy oncolytics · 2020Article
- A novel mutation in the mouse Pcsk1 gene showing obesity and diabetes.Mammalian genome : official journal of the International Mammalian Genome Society · 2020Article
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- Paclitaxel Treatment and Proprotein Convertase 1/3 (PC1/3) Knockdown in Macrophages is a Promising Antiglioma Strategy as Revealed by Proteomics and Cytotoxicity Studies.Molecular & cellular proteomics : MCP · 2018Article
- Article
- Proprotein convertase 1/3 inhibited macrophages: A novel therapeutic based on drone macrophages.EuPA open proteomics · 2016Article
- The proprotein convertase PC1/3 regulates TLR9 trafficking and the associated signaling pathways.Scientific reports · 2016Article
- Molecular Consequences of Proprotein Convertase 1/3 (PC1/3) Inhibition in Macrophages for Application to Cancer Immunotherapy: A Proteomic Study.Molecular & cellular proteomics : MCP · 2015Article
- The proprotein convertase subtilisin/kexin furinA regulates zebrafish host response against Mycobacterium marinum.Infection and immunity · 2015Article
- Proprotein convertase FURIN constrains Th2 differentiation and is critical for host resistance against Toxoplasma gondii.Journal of immunology (Baltimore, Md. : 1950) · 2014Article
- Genetics of the first seven proprotein convertase enzymes in health and disease.Current genomics · 2013Article
- Differential processing of neuropeptide proprotein in human breast adenocarcinoma.Journal of endocrinological investigation · 2013Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
Abstract
The proprotein convertase 1/3 is expressed in the regulated secretory pathway of neural and endocrine cells. Its major function is in the post-translational processing and activation of precursor proteins. The PC1/3 knock-out (KO) mouse model has allowed us to elucidate its physiological functions in studies focused primarily on neuroendocrine tissues. However, PC1/3 is also expressed in cells of the immune system, mainly in macrophages. The present study explores the effects of innate immune challenge in the PC1/3 KO mouse. PC1/3 KO mice have an enlarged spleen with marked disorganization of the marginal zone and red pulp. Immunohistochemical studies using various markers demonstrate a depletion of dendritic cells in PC1/3 KO spleens. When challenged with lipopolysaccharide, PC1/3 KO mice are more susceptible to septic shock than wild-type controls or other PC KO mice, such as PC2 and PC7 null mice. Plasma levels of proinflammatory cytokines (IL-6, IL-1β, and TNF-α) were very significantly elevated in PC1/3 KO mice, consistent with a hypercytokinemia, i.e. indicative of a major systemic uncontrolled inflammatory response or cytokine storm. Peritoneal macrophages isolated from PC1/3 KO mice also demonstrate elevated cytokine secretion when treated with LPS. Electron micrographs show morphological features indicating a prolonged activation of these cells following LPS stimulation. We also present evidence that the proinflammatory T(h)1 pathway is dominant in the PC1/3 KO mouse model. We conclude that aside from its important role in neuroendocrine functions PC1/3 also has an important role in the regulation of the innate immune system, most likely through the regulation of cytokine secretion in macrophages.
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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.