Cyanidin attenuates IL-17A cytokine signaling mediated monocyte migration and differentiation into mature osteoclasts in rheumatoid arthritis.

Abstract

Interleukin (IL)-17A signaling pathway plays a critical role in the initiation and progression of rheumatoid arthritis (RA) and represents a viable target for RA therapy. Cyanidin, a flavonoid compound, is a novel inhibitor of IL-17A/IL-17RA (receptor subunit A) interaction in several inflammatory diseases. However, the therapeutic efficacy of cyanidin on IL-17A cytokine signaling induced monocyte migration and fibroblast-like synoviocytes (FLS) released RANKL mediated osteoclastogenesis in RA has not yet been deciphered. In the present study, cyanidin impeded IL-17A induced migration of monocytes isolated from adjuvant-induced arthritic (AA) rats. At the molecular level, cyanidin blocked the activation of p38MAPK signaling in response to IL-17A. Importantly, cyanidin downregulated IL-17A induced expression of HSP27, CXCR4, and CCR7 in AA monocytes via modulating IL-17/p38 MAPK signaling axis. Alternatively, cyanidin significantly suppressed the formation of matured osteoclasts and bone resorption in a coculture system consisting of IL-17 treated AA-FLS and rat bone marrow-derived monocytes/macrophages. Further, cyanidin significantly inhibited the expression of RANKL and increased the expression of OPG in AA-FLS via blunted activation of IL-17A/STAT-3 signaling cascade. Interestingly, cyanidin impaired IL-17A induced overexpression of IL-17RA. Taken together, our study proposes a novel therapeutic function of cyanidin towards targeted inhibition of IL-17A/IL-17RA signaling mediated disease severity and bone erosion in RA.

• Authors: Snigdha Samarpita, Mahaboobkhan Rasool
• Journal: Cytokine (Cytokine) Vol. 142 Pg. 155502 (06 2021) ISSN: 1096-0023 [Electronic] England
• PMID: 33810944 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Elsevier Ltd. All rights reserved.

Chemical References

• Anthocyanins
• Ccr7 protein, rat
• HSP27 Heat-Shock Proteins
• Interleukin-17
• Osteoprotegerin
• RANK Ligand
• Receptors, CCR7
• Receptors, CXCR4
• Receptors, Interleukin-17
• STAT3 Transcription Factor
• Small Molecule Libraries
• cyanidin
• p38 Mitogen-Activated Protein Kinases

Topics

• Animals
• Anthocyanins (chemistry, pharmacology)
• Arthritis, Experimental (pathology)
• Arthritis, Rheumatoid (complications, pathology)
• Bone Resorption (complications, pathology)
• Cell Differentiation (drug effects)
• Cell Movement (drug effects)
• Cell Survival (drug effects)
• Down-Regulation (drug effects)
• Female
• HSP27 Heat-Shock Proteins (metabolism)
• Interleukin-17 (metabolism)
• Male
• Mice
• Models, Biological
• Monocytes (drug effects, metabolism, pathology)
• Osteoclasts (drug effects, metabolism, pathology)
• Osteogenesis (drug effects)
• Osteoprotegerin (metabolism)
• Phosphorylation (drug effects)
• RANK Ligand (metabolism)
• Rats, Wistar
• Receptors, CCR7 (metabolism)
• Receptors, CXCR4 (metabolism)
• Receptors, Interleukin-17 (metabolism)
• STAT3 Transcription Factor (metabolism)
• Signal Transduction (drug effects)
• Small Molecule Libraries (pharmacology)
• p38 Mitogen-Activated Protein Kinases (metabolism)
• Rats