Eotaxin-1/CCL11 is involved in cell migration in rheumatoid arthritis

Kuninobu Wakabayashi,Sayaka Fukuse,Takeo Isozaki,Yumi Tsubokura,Tsuyoshi Kasama

doi:10.1038/s41598-021-87199-7

Kuninobu Wakabayashi, Sayaka Fukuse + Show 3 more

Open Access

https://doi.org/10.1038/s41598-021-87199-7

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Journal: Scientific Reports	Publication Date: Apr 12, 2021
Citations: 15	License type: open-access

Affiliation: Showa University

Abstract

Eotaxin-1 (CCL11) induces the migration of different leukocyte types by interacting with CCR3. In rheumatoid arthritis (RA), fibroblast-like synoviocytes (FLS) are pathogenic effectors and a major CCR3-expressing cell. The aim of this study was to investigate the expression and function of CCL11 in RA FLS. The expression of CCL11 and CCR3 was evaluated by ELISA, immunofluorescence and quantitative PCR analysis. The CCL11 levels in serum and synovial fluids (SFs) from RA patients were significantly higher than those in serum from healthy controls and SFs from osteoarthritis patients. CCL11 and CCR3 were expressed in the RA synovial tissue lining layers. The secretion of CCL11 in RA FLS-conditioned medium and the mRNA expression of CCL11 and CCR3 were induced by TNF-α. Furthermore, CCL11 induced the mRNA expression of CCL11 and CCR3. Application of a CCR3 antagonist reduced TNF-α-induced CCL11 secretion from RA FLS. CCL11 induced the migration of RA FLS and monocytes. RA FLS migration was decreased by treatment with CCL11 siRNA. The migration of monocytes to medium conditioned with CCL11 siRNA-transfected and TNF-α-stimulated RA FLS was reduced. These data indicate that the self-amplification of CCL11 via CCR3 may play an important role in cell migration in RA.

Highlights

Eotaxin-1 (CCL11) induces the migration of different leukocyte types by interacting with CCR3
We investigated the levels of C–C motif ligand 11 (CCL11) in serum and synovial fluids (SFs) at the onset of rheumatoid arthritis (RA) using Enzyme‐linked immunosorbent assay (ELISA)
We measured the levels of tumor necrosis factor-α (TNF-α) and a few major CC-chemokines, CCL2, CCL3, and CCL5, whose expression was increased by TNFα from RA FLS22,23

Summary

Introduction

Eotaxin-1 (CCL11) induces the migration of different leukocyte types by interacting with CCR3. The migration of monocytes to medium conditioned with CCL11 siRNA-transfected and TNF-α-stimulated RA FLS was reduced. These data indicate that the self-amplification of CCL11 via CCR3 may play an important role in cell migration in RA. The expression of CCL11 on epithelial cells and fibroblasts has been investigated, and it has been shown that CCL11 is induced by pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α)[7,8,9]. A recent study revealed that the receptor activator of nuclear factor kappa-B ligand stimulated CCR3 expression in osteoclasts and that the addition of CCL11 caused an increased migration of preosteoclasts and an increase in osteoclastic bone resorption[21]. The aim of this study was to investigate the expression and function of CCL11 and its relationship to other CC chemokines in RA FLS

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