Naringenin inhibits dendritic cell maturation and has therapeutic effects in a murine model of collagen-induced arthritis.
The aim of this study was to investigate the effect of naringenin (5,7,4'-trihydroxyflavanone), a citrus flavonoid, on dendritic cell (DC) maturation, as well as its potential as a therapeutic agent in a murine model of collagen-induced arthritis (CIA). Naringenin effectively inhibited lipopolysaccharide (LPS)-induced DC maturation as shown by reductions in the production of proinflammatory cytokines/chemokines, the expression of costimulatory molecules and the Ag-specific T cell priming ability of DCs when given at noncytotoxic doses. In addition, the decrease of LPS-induced MAPK and NF-κB signaling activation may contribute to the inhibitory activity of naringenin. In mice with CIA, the oral administration of naringenin ameliorated the severity of arthritis, reduced the levels of anticollagen Type II (CII) IgG and limited the proliferation of T cells, observed as a lower frequency of Th1 and Th17 cells in the spleen after restimulation with CII. In conclusion, this study shows for the first time that naringenin can manipulate the immunostimulatory properties of DCs and thus represents a potential therapeutic for the treatment of rheumatoid arthritis in humans.
Institute of Biomedical Science and Rong Hsing Research Center for Translational Medicine, National Chung-Hsing University, Taichung, Taiwan.
Yi-Rong
YR
Li
Institute of Biomedical Science and Rong Hsing Research Center for Translational Medicine, National Chung-Hsing University, Taichung, Taiwan; Department of Medical Research and Education, Taichung Veterans General Hospital, Taichung, Taiwan.
Der-Yuan
DY
Chen
Graduate Institute of Immunology, National Taiwan University, Taipei, Taiwan.
Ching-Liang
CL
Chu
Department of Food Science, Rutgers University, New Brunswick, NJ, USA; Colleage of Chemistry and Chemical Engineering, Huanggang Normal University, Hubei, China.
Shiming
S
Li
Department of Food Science, National Pingtung University of Science and Technology, Pingtung, Taiwan.
Yu-Kuo
YK
Chen
Department of Biochemistry and Molecular Biology, National Cheng Kung University Medical College, Tainan, Taiwan.
Chao-Ling
CL
Wu
Institute of Biomedical Science and Rong Hsing Research Center for Translational Medicine, National Chung-Hsing University, Taichung, Taiwan; Department of Medical Research and Education, Taichung Veterans General Hospital, Taichung, Taiwan. Electronic address: lincc@dragon.nchu.edu.tw.
Chi-Chen
CC
Lin
D000284:Administration, Oral; D000818:Animals; D001169:Arthritis, Experimental / Q000378:metabolism*; D001172:Arthritis, Rheumatoid / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D049109:Cell Proliferation; D002470:Cell Survival; D003094:Collagen / Q000009:adverse effects*; D003713:Dendritic Cells / Q000166:cytology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D044950:Flavanones / Q000737:chemistry*; D007074:Immunoglobulin G / Q000097:blood; D007249:Inflammation; D008024:Ligands; D008070:Lipopolysaccharides / Q000737:chemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000378:metabolism; D015398:Signal Transduction; D013154:Spleen / Q000378:metabolism; D018417:Th1 Cells / Q000166:cytology; D058504:Th17 Cells / Q000166:cytology
D044950:Flavanones; D007074:Immunoglobulin G; D008024:Ligands; D008070:Lipopolysaccharides; D016328:NF-kappa B; D003094:Collagen; C005273:naringenin
Collagen-induced arthritis; Dendritic cells; Flavonoid; Maturation; Naringenin