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Abstract Number: 0026

Synovial Fibroblasts Acquire a Proinflammatory and Destructive Phenotype After Exposure to αS1-Casein (CSN1S1)

Nadine Honke1, Tim Appel1, Matthias Schneider2 and Georg Pongratz3, 1Department of Rheumatology, Hiller Research Center Rheumatology, University Hospital Düsseldorf, Germany (* contributed equally), Düsseldorf, Germany, 2Policlinic & Hiller Research Unit Rheumatology, UKD, Heinrich-Heine University, Düsseldorf, Germany, 3Polyclinic and Functional Area for Rheumatology & Hiller Research Center Rheumatology, University Hospital Düsseldorf, Düsseldorf, Germany

Meeting: ACR Convergence 2021

Keywords: Fibroblasts, Synovial, Interleukins, Metalloproteinase, Osteoarthritis, rheumatoid arthritis

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Session Information

Date: Saturday, November 6, 2021

Session Title: RA – Etiology & Pathogenesis Poster (0011–0045)

Session Type: Poster Session A

Session Time: 8:30AM-10:30AM

Background/Purpose: 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 and OA synovial fibroblasts (RASF and OASF).

Methods: Fibroblasts were isolated from synovial tissues obtained from patients diagnosed with RA and OA who underwent synovectomy due to total joint replacement. RASF and OASF 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 and OA 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=5-6, RA: p***=0.0001; OA: p**=0.0048), IL-8 (Ctrl. vs. αS1-Casein (500ng/ml); n=5, RA: p****< 0.0001; OA: p*=0.0179) and MMP3 (Ctrl. vs. αS1-Casein (500ng/ml); n=5-6, RA: p***=0.0007; OA: n.s.). LPS treatment alone increased the levels of IL-6 (Ctrl. vs. LPS 1ng/ml; n=5-6, RA: p*=0.0455, OA: n.s.; Ctrl. vs. LPS 10ng/ml; n=5-6, RA: p**=0.0039; OA: p**=0.0014), IL-8 (Ctrl. vs. LPS 1ng/ml; n=4-5, RA: p**=0.0037, OA: p**=0,0094; Ctrl. vs. LPS 10ng/ml; n=4-5, RA: p***=0.0005; OA: p***=0.0002) and MMP3 (Ctrl. vs. LPS 1ng/ml; n=5-6, RA: n.s; OA: p*=0.0433; Ctrl. vs. LPS 10ng/ml; n=5-6, RA: p*=0,0287; OA: p**=0.002). Addition of polymyxin B 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, RA: p*=0.0326; OA: p*=0.014; IL-8: LPS 10ng/ml vs. LPS 10ng/ml +Px5, n=5-6, RA: p**=0.0038; OA: p****< 0.0001; MMP3: LPS 10ng/ml vs. LPS 10ng/ml +Px5, n=6, RA: p*=0.0287; OA: n.s.). Furthermore, by using immunofluorescence histology of synovial tissue from RA and OA patients, we demonstrated that infiltration of casein-positive cells occurs mainly in RA and not OA patients.

Conclusion: In conclusion, our results suggest that casein-positive infiltrating cells are responsible for inducing a proinflammatory phenotype in RASF and augment their destructive capability. αS1-Casein might therefore be part of the pathomechanism of RA.


Disclosures: N. Honke, None; T. Appel, None; M. Schneider, GlaxoSmithKline, 2, 5, 6, UCB, 5, 6, AbbVie, 2, 5, Alexion, 2, AstraZeneca, 2, 6, Boehringer-Ingelheim, 2, Janssen-Cilag, 2, 6, Lilly, 2, 6, Novartis, 2, Pfizer, 2, 6, Roche, 2, Sanofi-Aventis, 2, Biogen, 6, BMS, 6, Celgene, 6, Chugai, 6; G. Pongratz, None.

To cite this abstract in AMA style:

Honke N, Appel T, Schneider M, Pongratz G. Synovial Fibroblasts Acquire a Proinflammatory and Destructive Phenotype After Exposure to αS1-Casein (CSN1S1) [abstract]. Arthritis Rheumatol. 2021; 73 (suppl 9). https://acrabstracts.org/abstract/synovial-fibroblasts-acquire-a-proinflammatory-and-destructive-phenotype-after-exposure-to-%ce%b1s1-casein-csn1s1/. Accessed January 28, 2023.
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