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

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

doi:10.3389/fphar.2021.721594

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

Front Pharmacol. 2021 Oct 5:12:721594. doi: 10.3389/fphar.2021.721594. eCollection 2021.

Authors

Chien-Fu Chen^{1

2}, Hsin-Pei Li¹, Ya-Hsuan Chao³, Min-Yu Tu^{4

5

6}, Chih-Ching Yen^{1

7}, Ying-Wei Lan¹, Shang-Hsun Yang⁸, Kowit-Yu Chong^{9

10}, Chi-Chien Lin³, Chuan-Mu Chen^{1

11}

Affiliations

¹ Department of Life Sciences, and Ph.D. Program in Translational Medicine, College of Life Sciences, National Chung Hsing University, Taichung, Taiwan.
² Department of Orthopedic Surgery, Taichung Armed Forces General Hospital, Taichung, Taiwan.
³ Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan.
⁴ Kaohsiung Armed Forces General Hospital Gangshan Branch, Kaohsiung, Taiwan.
⁵ Department of Health Business Administration, Meiho University, Pingtung, Taiwan.
⁶ Institute of Medical Science and Technology, National Sun Yat-Sen University, Kaohsiung, Taiwan.
⁷ Department of Internal Medicine, China Medical University Hospital, and College of Health Care, China Medical University, Taichung, Taiwan.
⁸ Department of Physiology, and Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
⁹ Department of Medical Biotechnology and Laboratory Science and Graduate Institute of Biomedical Sciences, Division of Biotechnology, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
¹⁰ Hyperbaric Oxygen Medical Research Lab, Bone and Joint Research Center, and Department of Laboratory Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
¹¹ The iEGG and Animal Biotechnology Center, and the Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan.

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.

Keywords: CD4+ T cells; bone marrow-derived dendritic cells; collagen-induced arthritis; kefir peptides; rheumatoid arthritis.