Bruton's tyrosine kinase regulates TLR7/8-induced TNF transcription via nuclear factor-κB recruitment
| Autor: | Page, TH, Urbaniak, AM, Espirito Santo, AI, Danks, L, Smallie, T, Williams, LM, Horwood, NJ |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Biochemistry & Molecular Biology
Transcription Genetic Biophysics Down-Regulation R848 0601 Biochemistry and Cell Biology Article ACTIVATION hemic and lymphatic diseases Agammaglobulinaemia Tyrosine Kinase Humans NF kappa B Phosphorylation Promoter Regions Genetic 3' Untranslated Regions Base Pairing ALPHA PRODUCTION Cell Nucleus Science & Technology INHIBITOR IBRUTINIB RECEPTOR 0304 Medicinal and Biomolecular Chemistry Tumor Necrosis Factor-alpha Macrophages X-LINKED AGAMMAGLOBULINEMIA NF-kappa B Transcription Factor RelA CYTOKINE PRODUCTION Protein-Tyrosine Kinases BTK INHIBITOR Bruton's tyrosine kinase Toll-like receptors-7/8 Toll-Like Receptor 4 TEC FAMILY KINASES Toll-Like Receptor 7 1101 Medical Biochemistry and Metabolomics Toll-Like Receptor 8 CELLS Cytokines Life Sciences & Biomedicine NFκB |
| Zdroj: | Biochemical and Biophysical Research Communications |
| Popis: | Tumour necrosis factor (TNF) is produced by primary human macrophages in response to stimulation by exogenous pathogen-associated molecular patterns (PAMPs) and endogenous damage-associated molecular patterns (DAMPs) via Toll-like receptor (TLR) signalling. However, uncontrolled TNF production can be deleterious and hence it is tightly controlled at multiple stages. We have previously shown that Bruton's tyrosine kinase (Btk) regulates TLR4-induced TNF production via p38 MAP Kinase by stabilising TNF messenger RNA. Using both gene over-expression and siRNA-mediated knockdown we have examined the role of Btk in TLR7/8 mediated TNF production. Our data shows that Btk acts in the TLR7/8 pathway and mediates Ser-536 phosphorylation of p65 RelA and subsequent nuclear entry in primary human macrophages. These data show an important role for Btk in TLR7/8 mediated TNF production and reveal distinct differences for Btk in TLR4 versus TLR7/8 signalling. Highlights • Btk is required for TLR7/8 signalling in primary human macrophages. • R848-induced TNF mRNA is more Btk dependent than LPS-induced TNF mRNA. • Btk transcriptional control of TNF following R848 requires the promoter and 3′UTR. • Btk knockdown reduces p65RelA translocation to the nucleus upon TLR7/8 stimulation. |
| Databáze: | OpenAIRE |
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