CCL22 induces pro-inflammatory changes in fibroblast-like synoviocytes

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. [Display omitted] •CCL22 increases the expression of the pro-inflammatory mediator S100A12•CCL22 decreases the expression of anti-inflammatory mediators IL-4 and IL-10•Fibroblast-like synoviocytes from normal and OA joints do not express CCR4•CCL22 induces S100A12 expression through CCR3 but not CCR5 Molecular Biology; Immunology