CCL22 induces pro-inflammatory changes in fibroblast-like synoviocytes

Guomin Ren; Nedaa Al-Jezani; Pamela Railton; James N Powell; Roman J Krawetz

doi:10.1016/j.isci.2020.101943

CCL22 induces pro-inflammatory changes in fibroblast-like synoviocytes

iScience. 2020 Dec 13;24(1):101943. doi: 10.1016/j.isci.2020.101943. eCollection 2021 Jan 22.

Authors

Guomin Ren^{1

2}, Nedaa Al-Jezani¹, Pamela Railton³, James N Powell^{1

4}, Roman J Krawetz^{1

2

4

5}

Affiliations

¹ McCaig Institute for Bone & Joint Health, Faculty of Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary, AB T2N 4N1, Canada.
² University of Calgary, Biomedical Engineering Graduate Program, Calgary, AB T2N 4N1, Canada.
³ Charles Sturt University, School of Biomedical Science, Wagga Wagga, NSW 2650, Australia.
⁴ University of Calgary, Department of Surgery, Calgary, AB T2N 4N1, Canada.
⁵ University of Calgary, Department of Anatomy and Cell Biology, Calgary, AB T2N 4N1, Canada.

Abstract

Synovitis is common in patients with osteoarthritis (OA) and is associated with pain and disease progression. We have previously demonstrated that the chemokine C-C motif chemokine 22 (CCL22) induces chondrocyte apoptosis in vitro; however, the effects of CCL22 on the synovium remain unknown. Therefore, our goal was to investigate the effect of CCL22 on fibroblast-like synoviocytes (FLS). CCL22 treatment suppressed expression of IL-4 and IL-10 and promoted expression of S100A12 in FLS. The response of FLS to CCL22 was not dependent on the disease state of the joint (e.g., normal versus OA), but was instead correlated with the individuals' synovial fluid level of CCL22. CCL22 induction of S100A12 in FLS was attenuated after knockdown of CCR3, yet ligands of CCR3 (CCL7, CCL11) did not induce S100A12 expression. In the presence of CCL22, CCR3-positive FLS upregulate CCL22 and S100A12 driving a potential feedforward pro-inflammatory mechanism distinct from canonical CCL22 and CCR3 pathways.

Keywords: Immunology; Molecular Biology.