Back to Search
Start Over
Induction of pro-inflammatory cytokines by 29-kDa FN-f via cGAS/STING pathway
- Source :
- BMB Reports
- Publication Year :
- 2019
- Publisher :
- Korean Society for Biochemistry and Molecular Biology, 2019.
-
Abstract
- The cGAS-STING pathway plays an important role in pathogen-induced activation of the innate immune response. The 29-kDa amino-terminal fibronectin fragment (29-kDa FN-f) found predominantly in the synovial fluid of osteoarthritis (OA) patients increases the expression of catabolic factors via the toll-like receptor-2 (TLR-2) signaling pathway. In this study, we investigated whether 29-kDa FN-f induces inflammatory responses via the cyclic GMP-AMP synthase (cGAS)/stimulator of interferon gene (STING) pathway in human primary chondrocytes. The levels of cGAS and STING were elevated in OA cartilage compared with normal cartilage. Long-term treatment of chondrocytes with 29-kDa FN-f activated the cGAS/STING pathway together with the increased level of gamma-H2AX, a marker of DNA breaks. In addition, the expression of pro-inflammatory cytokines, including granulocytemacrophage colony-stimulating factor (GM-CSF/CSF-2), granulocyte colony-stimulating factor (G-CSF/CSF-3), and type I interferon (IFN-α), was increased more than 100-fold in 29-kDa FN-f-treated chondrocytes. However, knockdown of cGAS and STING suppressed 29-kDa FN-f-induced expression of GM-CSF, G-CSF, and IFN-α together with the decreased activation of TANK-binding kinase 1 (TBK1), interferon regulatory factor 3 (IRF3), and inhibitor protein κBα (IκBα). Furthermore, NOD2 or TLR-2 knockdown suppressed the expression of GM-CSF, G-CSF, and IFN-α as well as decreased the activation of the cGAS/STING pathway in 29-kDa FN-f-treated chondrocytes. These data demonstrate that the cGAS/STING/TBK1/IRF3 pathway plays a critical role in 29-kDa FN-f-induced expression of pro-inflammatory cytokines. [BMB Reports 2019; 52(5): 336-341].
- Subjects :
- medicine.medical_treatment
Primary Cell Culture
Cartilage metabolism
Protein Serine-Threonine Kinases
Biochemistry
Proinflammatory cytokine
03 medical and health sciences
Chondrocytes
Osteoarthritis
Synovial Fluid
medicine
Humans
Molecular Biology
Cytokine
Fibronectin fragments
0303 health sciences
Chemistry
030302 biochemistry & molecular biology
Membrane Proteins
General Medicine
Articles
DNA
Interferon-beta
Molecular biology
Nucleotidyltransferases
Toll-Like Receptor 2
Fibronectins
Sting
IκBα
Cartilage
Cytokines
Interferon Regulatory Factor-3
Signal transduction
IRF3
Interferon regulatory factors
cGAS
STING
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 1976670X and 19766696
- Volume :
- 52
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- BMB Reports
- Accession number :
- edsair.doi.dedup.....2478d52e4571b0e33d0a92853ca7ce8b