title: Oral Administration of 4-Hydroxy-3-Methoxycinnamaldehyde Attenuates Atopic Dermatitis by Inhibiting T Cell and Keratinocyte Activation.
abstract: Atopic dermatitis (AD) is a skin condition caused by an imbalance of distinct subsets of T helper cells. Previously, we showed that 4-hydroxy-3-methoxycinnamaldehyde (4H3MC) inhibits T cell activation but does not induce apoptosis. Here, we examined the mechanism underlying the inhibitory effect of 4H3MC on AD both in vivo and in vitro. We sought to test the pharmacological effects of 4H3MC using a mouse model of 2, 4-'2,4-dinitrocholorobenzene' (DNCB)- and mite-induced AD. Also, we determined whether 4H3MC affects T cell differentiation and proliferation. Oral administration of 4H3MC attenuated the symptoms of DNCB- and mite-induced AD, including increased ear thickness, serum IgE levels, immune cell infiltration into inflammatory lesions, and pathogenic cytokine expression in ear tissues. In vitro, 4H3MC blocked T cell differentiation into Th1 and Th2 subtypes, as reflected by suppression of T-bet and GATA3, which are key transcription factors involved in T cell differentiation. In addition, 4H3MC downregulated T cell proliferation during Th1 and Th2 differentiation and keratinocyte activation. Collectively, these findings suggest that 4H3MC ameliorates AD symptoms by modulating the functions of effector T cells and keratinocytes.
authors.affiliation: School of Life Sciences, Immune Synapse Research Center and Cell Dynamics Research Center, Gwangju Institute of Science and Technology, Gwangju, Republic of Korea.
authors.forename: Hyun-Su
authors.initials: HS
authors.lastname: Lee
authors.affiliation: Division of Sport Science, College of Natural Sciences, Konkuk University, Chungju, Republic of Korea.
authors.forename: Eun-Ju
authors.initials: EJ
authors.lastname: Choi
authors.affiliation: Division of Sport Science, College of Natural Sciences, Konkuk University, Chungju, Republic of Korea.
authors.forename: Heeri
authors.initials: H
authors.lastname: Choi
authors.affiliation: School of Life Sciences, Immune Synapse Research Center and Cell Dynamics Research Center, Gwangju Institute of Science and Technology, Gwangju, Republic of Korea.
authors.forename: Kyung-Sik
authors.initials: KS
authors.lastname: Lee
authors.affiliation: School of Life Sciences, Immune Synapse Research Center and Cell Dynamics Research Center, Gwangju Institute of Science and Technology, Gwangju, Republic of Korea.
authors.forename: Hye-Ran
authors.initials: HR
authors.lastname: Kim
authors.affiliation: School of Life Sciences, Immune Synapse Research Center and Cell Dynamics Research Center, Gwangju Institute of Science and Technology, Gwangju, Republic of Korea.
authors.forename: Bo-Ra
authors.initials: BR
authors.lastname: Na
authors.affiliation: School of Life Sciences, Immune Synapse Research Center and Cell Dynamics Research Center, Gwangju Institute of Science and Technology, Gwangju, Republic of Korea.
authors.forename: Min-Sung
authors.initials: MS
authors.lastname: Kwon
authors.affiliation: College of Pharmacy, Keimyung University, Daegu, Republic of Korea.
authors.forename: Gil-Saeng
authors.initials: GS
authors.lastname: Jeong
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsan, Republic of Korea.
authors.forename: Hyun Gyu
authors.initials: HG
authors.lastname: Choi
authors.affiliation: Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Choi
authors.affiliation: School of Life Sciences, Immune Synapse Research Center and Cell Dynamics Research Center, Gwangju Institute of Science and Technology, Gwangju, Republic of Korea.
authors.forename: Chang-Duk
authors.initials: CD
authors.lastname: Jun
mesh_terms: D000171:Acrolein / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000284:Administration, Oral; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000276:immunology / Q000517:prevention & control*; D004137:Dinitrochlorobenzene / Q000276:immunology; D005260:Female; D050990:GATA3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D018836:Inflammation Mediators / Q000378:metabolism; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008925:Mites / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D018417:Th1 Cells / Q000187:drug effects / Q000378:metabolism; D018418:Th2 Cells / Q000187:drug effects / Q000378:metabolism; D000098815:T-bet Transcription Factor
chemical_list: D016207:Cytokines; D004137:Dinitrochlorobenzene; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D018836:Inflammation Mediators; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; C075384:coniferaldehyde; D000171:Acrolein