title: Dehydrodiconiferyl alcohol (DHCA) modulates the differentiation of Th17 and Th1 cells and suppresses experimental autoimmune encephalomyelitis.
abstract: Dehydrodiconiferyl alcohol (DHCA), originally isolated from the stems of Cucurbita moschata, has previously been shown to exhibit anti-adipogenic and anti-lipogenic effects in 3T3-L1 cells and primary mouse embryonic fibroblasts (MEFs) (Lee et al., 2012). Here, we investigated whether synthetic DHCA could suppress the CD4 T helper 17 (Th17)-mediated production of the interleukin (IL)-17 protein. The results from RT-qPCR suggest that DHCA-mediated down-regulation of IL-17 occurred at the transcriptional level by suppressing the expression of RAR-related orphan receptor (ROR)γt, the master transcription factor involved in the differentiation of Th17 cells. Furthermore, such inhibition was mediated by the suppression of NF-κB activity. DHCA also inhibited the Th1-mediated production of interferon (IFN) γ by controlling the expression of a key transcription factor known to regulate the production of this cytokine, T-bet. In the mouse experimental autoimmune encephalomyelitis (EAE) model, DHCA showed significant therapeutic effects by inhibiting the infiltration of immune cells into the spinal cords, decreasing the differentiation of pathogenic Th17 and Th1 cells, suppressing the expression of various pro-inflammatory cytokines, and eventually ameliorating the clinical symptoms of EAE mice. Taken together, our data indicate that DHCA may be a potential candidate as an agent for the control of Th17 and Th1-mediated inflammatory diseases.
authors.affiliation: Department of Biological Sciences, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Junghun
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Biological Sciences, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Jinyong
authors.initials: J
authors.lastname: Choi
authors.affiliation: Department of Biological Sciences, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Wonwoo
authors.initials: W
authors.lastname: Lee
authors.affiliation: Department of Biological Sciences, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Kyeongryang
authors.initials: K
authors.lastname: Ko
authors.affiliation: Department of Biological Sciences, Seoul National University, Seoul 151-742, Republic of Korea. Electronic address: sunyoung@snu.ac.kr.
authors.forename: Sunyoung
authors.initials: S
authors.lastname: Kim
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D028464:Cucurbita / Q000378:metabolism; D015536:Down-Regulation; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D020381:Interleukin-17 / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000096:biosynthesis; D010636:Phenols / Q000494:pharmacology* / Q000627:therapeutic use; D020825:T-Box Domain Proteins / Q000096:biosynthesis; D018417:Th1 Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D058504:Th17 Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D014158:Transcription, Genetic / Q000187:drug effects; D000098815:T-bet Transcription Factor
chemical_list: D020381:Interleukin-17; D016328:NF-kappa B; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D010636:Phenols; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; C080686:dehydrodiconiferyl alcohol; D007371:Interferon-gamma
keywords: Dehydrodiconiferyl alcohol (DHCA); EAE; IL-17; NF-κB; RORγt; Th1; Th17