Background/Purpose: Glycosylation has been reported to associate with tumor invasion and metastasis. Fucosylation is involved in the biological functions of adhesion molecules and growth factor receptors. In regards to arthritis, we have previously reported that glycan in rheumatoid arthritis (RA) serum was higher than that in normal subjects serum. However, a direct role for fucosylated cytokines in RA has not been demonstrated. Here, we examined fucosylated tumor necrosis factor (TNF)-α was expressed in RA synovial tissues, as TNF-α is a central cytokine in RA pathology and the role it plays in monocyte adhesion.

Methods:

To determine if the fucosylated TNF-α was expressed in RA and osteoarthritis (OA) synovial tissues, we performed immunofluorescence. In order to indicate that the expression of fucosylated TNF-α was in RA synovial fluids, immunoprecipitation and lectin blotting were performed. 2-deoxy-D-galactose (2-dGal) is an analog of hexose that inhibits fucosylation. In addition, to clarify the mechanism of fucosylation in monocyte adhesion, human umbilical vein endothelial cells (HUVECs) were treated with 2-dGal (15 mM) for 5 days. THP-1 (human acute monocyte leukemia cell line) adhesion to 2-dGal treated or nontreated HUVEC was measured. Finally, to confirm which adhesion molecules were involved in fucosylation, cell surface ELISA was performed.

Results: Fucosylated TNF-α was expressed in RA synovial tissues. Hence, fucosylated TNF-α in RA synovial tissues was significantly highly expressed compared with that in OA synovial tissues. Fucosylated TNF-α in RA synovial fluids was also significantly higher compared with in OA synovial fluids. Fucosylated proteins in 2-dGal treated HUVECs were decreased compared with these in nontreated HUVECs. Adhesion of THP-1 cells to 2-dGal treated HUVECs in response to TNF-α was significantly decreased compared with nontreated HUVECs (adhesion index of THP-1 to HUVECs ± SEM; 1.2 ± 0.1 and 1.4 ± 0.1, p<0.05, respectively). In addition, intercellular adhesion molecule 1 (ICAM-1) on TNF-α stimulated 2-dGal treated HUVECs were decreased compared to nontreated HUVECs (fold change of ICAM-1 expressed ± SEM; 5.5 ± 0.2 and 9.0 ± 0.2, p<0.05, respectively).

Conclusion: Fucosylated TNF-α was expressed in RA synovium, and inhibition of fucosylation in ECs had less monocyte adhesion. These data indicate that cytokine fucosylation is involved with RA and plays a role in inflammation, suggest that targeting fucosylation may provide a method by which to decrease inflammation.

« Back to 2018 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/fucosylated-tumor-necrosis-factor-%ce%b1-is-expressed-in-rheumatoid-arthritis-synovial-tissues-and-is-involved-in-monocyte-adhesion/