Cell reports (Cambridge), 2014-11, Vol.9 (3), p.910-917
2014
Details
- Autor(en) / Beteiligte
- Titel
- Granzyme A Produces Bioactive IL-1β through a Nonapoptotic Inflammasome-Independent Pathway
- Ist Teil von
- Cell reports (Cambridge), 2014-11, Vol.9 (3), p.910-917
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2014
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Bacterial components are recognized by the immune system through activation of the inflammasome, eventually causing processing of the proinflammatory cytokine interleukin-1β (IL-1β), a pleiotropic cytokine and one of the most important mediators of inflammation, through the protease caspase-1. Synthesis of the precursor protein and processing into its bioactive form are tightly regulated, given that disturbed control of IL-1β release can cause severe autoinflammatory diseases or contribute to cancer development. We show that the bacterial Pasteurella multocida toxin (PMT) triggers Il1b gene transcription in macrophages independently of Toll-like receptor signaling through RhoA/Rho-kinase-mediated NF-κΒ activation. Furthermore, PMT mediates signal transducer and activator of transcription (STAT) protein-controlled granzyme A (a serine protease) expression in macrophages. The exocytosed granzyme A enters target cells and mediates IL-1β maturation independently of caspase-1 and without inducing cytotoxicity. These findings show that macrophages can induce an IL-1β-initiated immune response independently of inflammasome activity. [Display omitted] •PMT triggers IL-1β transcription through RhoA/ROCK-activated NF-кB•Granzyme A is expressed in macrophages through STAT activation•Granzyme A cleaves IL-1β intracellularly into bioactive IL-1β•PMT stimulates IL-1β maturation through an inflammasome-independent pathway Bacterial components are recognized by the immune system through activation of the inflammasome, eventually causing processing of the proinflammatory cytokine interleukin-1β (IL-1β) through the protease caspase-1. Hildebrand et al. describe a mechanism that bypasses inflammasome activation. Instead, Pasteurella multocida toxin stimulates the expression of the serine protease granzyme A that mediates maturation of IL-1β into a bioactive cytokine.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2211-1247eISSN: 2211-1247DOI: 10.1016/j.celrep.2014.10.003Titel-ID: cdi_doaj_primary_oai_doaj_org_article_34638665148e4950ada9e6c7f331d29c
- Format
- –
- Schlagworte
- Animals, Apoptosis - drug effects, Bacterial Proteins - pharmacology, Bacterial Toxins - pharmacology, Caspase 1 - metabolism, Granzymes - metabolism, Humans, Inflammasomes - drug effects, Inflammasomes - metabolism, Interleukin-1beta - biosynthesis, Interleukin-1beta - genetics, Interleukin-1beta - metabolism, Janus Kinases - metabolism, Mice, NF-kappa B - metabolism, Perforin - metabolism, Protein Processing, Post-Translational - drug effects, rho-Associated Kinases - metabolism, rhoA GTP-Binding Protein - metabolism, Signal Transduction - drug effects, STAT Transcription Factors - metabolism, Toll-Like Receptors - metabolism, Transcription, Genetic - drug effects