Suppression of Dendritic Cell Maturation by Kefir Peptides Alleviates Collagen-Induced Arthritis in Mice.

Chien-Fu Chen,Chi‐Chien Lin,Chuan-Mu Chen,Shang-Hsun Yang,Kowit-Yu Chong,Hsin-Pei Li,Chih-Ching Yen,Ying-Wei Lan,Ya-Hsuan Chao,Min-Yu Tu

doi:10.3389/fphar.2021.721594

Abstract

Arthritis is a disorder that is characterized by joint inflammation and other symptoms. Rheumatoid arthritis (RA), an autoimmune disease, is one of the most common arthritis in worldwide. Inflammation of the synovium is the main factor that triggers bone erosion in the joints in RA, but the pathogenesis of RA is not clearly understood. Kefir grain-fermented products have been demonstrated to enhance immune function and exhibit immune-modulating bioactivities. This study aims to explore the role of kefir peptides (KPs) on the regulation of dendritic cell, which are found in RA synovial fluid, and the protection effects of KPs on mice with collagen-induced arthritis (CIA). Immature mouse bone marrow-derived dendritic cells (BMDCs) were treated with KPs (2.2 and 4.4 mg/ml) and then exposed to lipopolysaccharide (LPS) to study the immune regulation function of KPs in dendritic cells. Mice with CIA (n = 5 per group) were orally administrated KPs (3.75 and 7.5 mg/day/kg) for 21 days and therapeutic effect of KPs on mice with arthritis were assessed. In this study, we found that KPs could inhibit surface molecule expression, reduce inflammatory cytokine release, and repress NF-κB and MAPK signaling in LPS-stimulated mouse BMDCs. In addition, a high dose of KPs (7.5 mg/kg) significantly alleviated arthritis symptoms, decreased inflammatory cytokine expression, suppressed splenic DC maturation and decrease the percentage of Th1 and Th17 in the spleens on mice with CIA. Our findings demonstrated that KPs ameliorate CIA in mice through the mechanism of suppressing DC maturation and inflammatory cytokine releases.

Highlights

Arthritis is a chronic disorder that involves joint inflammation, and the related symptoms generally include joint pain and stiffness
Immature mouse bone marrow-derived dendritic cells (BMDCs) were treated with kefir peptides (KPs) (2.2 and 4.4 mg/ ml) and exposed to LPS which is a bacterial product known to induce Dendritic cells (DCs) maturation
Data showed that KP-treated alone at the high concentration (4.4 mg/ml) did not cause a notable change in immature mice BMDCs compared to vehicle control

Summary

Introduction

Arthritis is a chronic disorder that involves joint inflammation, and the related symptoms generally include joint pain and stiffness. OA is a painful condition caused by gradually mechanical wear and tear on joints, whereas RA is an autoimmune disease arising from an abnormal immune response in which patient’s own immune system attacks the joints (Parekh et al, 1985). The pathogenesis of RA is not clearly understood but may involve genomic variations, gene transcription, protein translation and posttranslational modifications (Song and Lin, 2017). The erosion of cartilage and bone is a classical feature of RA. One of the major factors that triggers cartilage and bone erosion in joints during RA progression is inflammation of the synovium (Chabaud et al, 2000; Won et al, 2011)

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