Granzymes A and K differentially potentiate LPS-induced cytokine response
Autor: | Niels Bovenschen, Annette C. Wensink, Jan Meeldijk, C. Erik Hack, Job Fermie, Helena M Kok, Christopher J. Froelich |
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Jazyk: | angličtina |
Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Cancer Research Proteases Lipopolysaccharide medicine.medical_treatment Immunology Inflammation Article 03 medical and health sciences Cellular and Molecular Neuroscience chemistry.chemical_compound 0302 clinical medicine Journal Article medicine Cytotoxic T cell Innate immune system biology Cell Biology Cell biology 030104 developmental biology Cytokine Granzyme chemistry 030220 oncology & carcinogenesis biology.protein Granzyme K lipids (amino acids peptides and proteins) medicine.symptom |
Zdroj: | Cell Death Discovery Cell death discovery, 2(1). Nature Publishing Group |
ISSN: | 2058-7716 |
Popis: | Granzymes are serine proteases that, upon release from cytotoxic cells, induce apoptosis in tumor cells and virally infected cells. In addition, a role of granzymes in inflammation is emerging. Recently, we have demonstrated that extracellular granzyme K (GrK) potentiates lipopolysaccharide (LPS)-induced cytokine response from monocytes. GrK interacts with LPS, disaggregates LPS micelles, and stimulates LPS-CD14 binding and Toll-like receptor signaling. Here we show that human GrA also potentiates cytokine responses in human monocytes initiated by LPS or Gram-negative bacteria. Similar to GrK, this effect is independent of GrA catalytic activity. Unlike GrK, however, GrA does not bind to LPS, has little influence on LPS micelle disaggregation, and does not augment LPS-CD14 complex formation. We conclude that GrA and GrK differentially modulate LPS-Toll-like receptor signaling in monocytes, suggesting functional redundancy among cytotoxic lymphocyte proteases in the anti-bacterial innate immune response. |
Databáze: | OpenAIRE |
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