title: Immunomodulation of phloretin by impairing dendritic cell activation and function.
abstract: Dietary compounds in fruits and vegetables have been shown to exert many biological activities. In addition to antioxidant effects, a number of flavonoids are able to modulate inflammatory responses. Here, we demonstrated that phloretin (PT), a natural dihydrochalcone found in many fruits, suppressed the activation and function of mouse dendritic cells (DCs). Phloretin disturbed the multiple intracellular signaling pathways in DCs induced by the Toll-like receptor 4 (TLR4) agonist lipopolysaccharide (LPS), including ROS, MAPKs (ERK, JNK, p38 MAPK), and NF-κB, and thereby reducing the production of inflammatory cytokines and chemokines. Phloretin also effectively suppressed the activation of DCs treated with different dosages of LPS or various TLR agonists. The LPS-induced DC maturation was attenuated by phloretin because the expression levels of the MHC class II and the co-stimulatory molecules were down-regulated, which then inhibited the LPS-stimulating DCs and the subsequent naïve T cell activation in a mixed lymphocyte reaction. Moreover, in vivo administration of phloretin suppressed the phenotypic maturation of the LPS-challenged splenic DCs and decreased the IFN-γ production from the activated CD4 T cells. Thus, we suggest that phloretin may potentially be an immunomodulator by impairing the activation and function of DCs and phloretin-contained fruits may be helpful in the improvement of inflammation and autoimmune diseases.
authors.affiliation: Institute of Biomedical Science, National Chung Hsing University, Taichung, Taiwan, Republic of China. lincc@dragon.nchu.edu.tw bechanning2000@yahoo.com.tw jouyuan22@gmail.com dychen@mail.vghtc.gov.tw.
authors.forename: Chi-Chen
authors.initials: CC
authors.lastname: Lin
authors.forename: Ching-Liang
authors.initials: CL
authors.lastname: Chu
authors.forename: Chin-Sheng
authors.initials: CS
authors.lastname: Ng
authors.forename: Ching-Yen
authors.initials: CY
authors.lastname: Lin
authors.forename: Der-Yuan
authors.initials: DY
authors.lastname: Chen
authors.forename: I-Hong
authors.initials: IH
authors.lastname: Pan
authors.forename: Kao-Jean
authors.initials: KJ
authors.lastname: Huang
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology*; D007155:Immunologic Factors / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010693:Phloretin / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology
chemical_list: D016207:Cytokines; D007155:Immunologic Factors; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D010693:Phloretin