The hyperplastic phenotype of fibroblast-like synoviocytes (FLSs) plays an important role for
synovitis, chronic
inflammation and joint destruction in
rheumatoid arthritis (RA).
Interleukin 17A (IL-17A), a signature pro-inflammatory
cytokine effectively influences the hyperplastic transformation of FLS cells and synovial pannus growth.
IL-17A cytokine signalling participates in RA pathology by regulating an array of pro-inflammatory mediators and osteoclastogenesis.
Cyanidin, a key
flavonoid inhibits IL-17A/
IL-17 receptor A (IL-17RA) interaction and alleviates progression and disease severity of
psoriasis and
asthma. However, the therapeutic efficacy of
cyanidin on
IL-17A cytokine signalling in RA remains unknown. In the present study,
cyanidin inhibited
IL-17A induced migratory and proliferative capacity of FLS cells derived from adjuvant-induced
arthritis (AA) rats.
Cyanidin treatment reduced
IL-17A mediated reprogramming of AA-FLS cells to overexpress IL-17RA. In addition, significantly decreased expression of
IL-17A dependent cyr61,
IL-23,
GM-CSF, and TLR3 were observed in AA-FLS cells in response to
cyanidin. At the molecular level,
cyanidin modulated IL-17/IL-17RA dependent JAK/STAT-3 signalling in AA-FLS cells. Importantly,
cyanidin activated PIAS3
protein to suppress STAT-3 specific transcriptional activation in AA-FLS cells.
Cyanidin treatment to AA rats attenuated clinical symptoms, synovial pannus growth, immune cell infiltration, and bone erosion.
Cyanidin reduced serum level of
IL-23 and
GM-CSF and expression of Cyr 61 and TLR3 in the synovial tissue of AA rats. Notably, the level of p-STAT-3
protein was significantly decreased in the synovial tissue of AA rats treated with
cyanidin. This study provides the first evidence that
cyanidin can be used as IL-17/17RA signalling targeting therapeutic drug for the treatment of RA and this need to be investigated in RA patients.