Artikel
Synovial fibroblasts acquire a proinflammatory and destructive phenotype after exposure to αS1-Casein (CSN1S1)
Suche in Medline nach
Autoren
-
Tim Appel
- Universitätsklinikum Düsseldorf, Poliklinik und Funktionsbereich für Rheumatologie, Hiller Forschungszentrum Rheumatologie, Düsseldorf
-
Nadine Honke
- Universitätsklinikum Düsseldorf, Poliklinik und Funktionsbereich für Rheumatologie, Hiller Forschungszentrum Rheumatologie, Düsseldorf
-
Matthias Schneider
- Universitätsklinikum Düsseldorf, Poliklinik und Funktionsbereich für Rheumatologie, Hiller Forschungszentrum Rheumatologie, Düsseldorf
-
Georg Pongratz
- Universitätsklinikum Düsseldorf, Poliklinik und Funktionsbereich für Rheumatologie, Hiller Forschungszentrum Rheumatologie, Düsseldorf
| Veröffentlicht: | 14. September 2021 |
|---|
Gliederung
Text
Introduction: The milk protein αS1-Casein (CSN1S1) was described to be overexpressed in synovial tissue of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Recently we were able to show that αS1-Casein is capable of inducing the secretion of proinflammatory cytokines in human monocytic cells. Since synovial fibroblasts are known to regulate propagation of inflammation and contribute to cartilage and bone destruction in RA, our aim was to investigate whether αS1-Casein increases the pathogenic potential of RA synovial fibroblasts (RASF).
Methods: Fibroblasts were isolated from synovial tissues obtained from patients diagnosed with RA who underwent synovectomy due to total joint replacement. RASF were cultivated in the presence or absence of procaryotic recombinant human αS1-Casein and LPS. Polymyxin B (5µg/ml, Px5) was added to cultured cells to rule out any LPS-effects. After 24 hours fibroblast-derived IL-6, IL-8 and MMP-3 were measured in the supernatant by ELISA.
Results: ELISA analysis showed that synovial fibroblasts from RA patients acquire a proinflammatory and destructive phenotype after treatment with αS1-Casein. This proinflammatory phenotype was induced by αS1-Casein in a concentration-dependent manner with elevated secretion of IL-6 (Ctrl. vs. αS1-Casein (500ng/ml); n=5, p***=0.0001), IL-8 (Ctrl. vs. αS1-Casein (500ng/ml); n=5, p****<0.0001) and MMP3 (Ctrl. vs. αS1-Casein (500ng/ml); n=6, p***=0.0007). LPS treatment alone increased the levels of IL-6 (Ctrl. vs. LPS 1ng/ml; n=5, p*=0.0455; Ctrl. vs. LPS 10ng/ml; n=5, p**=0.0039), IL-8 (Ctrl. vs. LPS 1ng/ml; n=5, p**=0.0037; Ctrl. vs. LPS 10ng/ml; n=5, p***=0.0005) and MMP3 (Ctrl. vs. LPS 1ng/ml; n=6, n.s; Ctrl. vs. LPS 10ng/ml; n=6, p*=0,0287). Addition of polymyxin B, to eliminate possible LPS contamination, to αS1-Casein-treated fibroblasts did not significantly influence the secretion of the investigated factors (IL-6, IL-8, MMP3: αS1-Casein vs. αS1-Casein+Px5, n=4-6) while polymyxin B completely blunted the LPS-induced secretion (IL-6: LPS 10ng/ml vs. LPS 10ng/ml +Px5, n=5, p*=0.0326; IL-8: LPS 10ng/ml vs. LPS 10ng/ml +Px5, n=5, p**=0.0038; MMP3: LPS 10ng/ml vs. LPS 10ng/ml +Px5, n=6, p*=0.0287).
Conclusion: In conclusion, our results indicate that human αS1-Casein induces a proinflammatory phenotype in synovial fibroblasts and augments destructive capability of RASF. αS1-Casein might therefore be part of the pathomechanism of RA.
Notes: Appel T & Honke N contributed equally to the abstract.
Disclosures: None declared
