Background/Purpose: Chemokine C-C motif ligand 11 (CCL11) also known as eotaxin-1 is a member of the CC chemokine family, which acts as a major chemoattractant of eosinophils and a stimulator of basophils. Eotaxin-1/CCL11 is produced by lymphocytes, eosinophils and monocytes/macrophages and interacts with C-C chemokine receptor 3 (CCR3). CCR3 is associated with numerous inflammatory conditions and a recent study has also suggested expression of CCR3 on fibroblast-like synoviocyte (FLS) in rheumatoid arthritis (RA). In this study, we investigate the expression and the role of eotaxin-1/CCL11 and CCR3 in RA.

Methods: The levels of eotaxin-1/CCL11 were determined in serum from healthy control (HC) and the patients with RA using enzyme-linked immunosorbent assay (ELISA). We also measured the levels of eotaxin-1/CCL11 and tumor necrosis factor α (TNF-α) in synovial fluids (SFs) from the patients with RA and osteoarthritis (OA) using ELISA. To investigate the expression of eotaxin-1/CCL11 on RA FLS, cells were left unstimulated or were stimulated for 12-, 24- and 48-hours with 50 ng/mL of TNF-α. After stimulation, the protein expression levels of eotaxin-1/CCL11 in TNF-α treated RA FLS conditioned medium were measured by ELISA and the messenger RNA (mRNA) expression of eotaxin-1/CCL11 and CCR3 in RA FLS were measured by quantitative polymerase chain reaction (qPCR) analysis. The expression of eotaxin-1/CCL11 on RA FLS was demonstrated by immunohistochemistry.

Results: The levels of eotaxin-1/CCL11 in the serum from RA were higher than those in the serum from HC [mean ± SEM; 76 ± 6 pg/mL (n=48) and 52 ± 9 pg/mL (n=31), p<0.05, respectively]. The levels of eotaxin-1/CCL11 in SFs from the patients with RA were higher than those in SFs from the patients with OA [mean ± SEM; 61 ± 24 pg/mL (n=43) and 9 ± 2 pg/mL (n=20), p<0.05, respectively] and were positively correlated with the levels of TNF-α (r=0.35, p<0.05). The expression of eotaxin-1/CCL11 mRNA and the secretion of eotaxin-1/CCL11 in RA FLS were time-dependently increased by TNF-α stimulation following 12-, 24- and 48-hours (p<0.05). The expression of CCR3 mRNA was also induced time-dependently by TNF-α stimulation (p<0.05). Furthermore, it was observed that the eotaxin-1/CCL11 mRNA expression was positively correlated with the CCR3 mRNA expression (r=0.89, p <0.01). In addition, we confirmed that the expression of eotaxin-1/CCL11 on RA FLS was increased with TNF-α stimulation using immunohistochemistry.

Conclusion: These data indicate that TNF-α induced production of eotaxin-1/CCL11 from RA FLS, suggesting that eotaxin-1/CCL11 and CCR3 may play an important role of inflammation in RA.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/tumor-necrosis-factor-%ce%b1-induces-production-of-eotaxin-1ccl11-from-fibroblast-like-synoviocyte-in-rheumatoid-arthritis/