title: Tryptanthrin ameliorates atopic dermatitis through down-regulation of TSLP.
abstract: Atopic dermatitis (AD) is a common skin disease that greatly worsens quality of life. Thymic stromal lymphopoietin (TSLP) plays a decisive role in the development of AD. The purpose of this study is to examine whether tryptanthrin (TR) would suppress AD through the regulation of TSLP. We analyzed the effect of TR on the level of TSLP from phorbol myristate acetate/calcium ionophore A23187-activated human mast cell line, HMC-1 cells, in 2,4-dinitrofluorobenzene-induced AD-like skin lesions of NC/Nga mice, and in anti-CD3/anti-CD28-stimulated splenocytes. TR significantly suppressed the level of intracellular calcium and the production and mRNA expression of TSLP through the blockade of receptor-interacting protein 2/caspase-1/nuclear factor-κB pathway in the activated HMC-1 cells. TR also significantly suppressed the levels of histidine decarboxylase and IL-1β. Furthermore, TR ameliorated clinical symptoms in the AD model. TR significantly reduced the levels of TSLP, IL-4, IFN-γ, IL-6, TNF-α, thymus and activation-regulated chemokine, and caspase-1 in AD skin lesions. Also, TR significantly reduced the serum levels of histamine and IL-4 in the AD model. Finally, TR significantly inhibited the production of IL-4, IFN-γ, and TNF-α from the stimulated splenocytes. Taken together, TR exhibits the potential to be a therapeutic agent for AD through down-regulation of TSLP.
authors.affiliation: Department of Pharmacology, College of Korean Medicine, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
authors.forename: Na-Ra
authors.initials: NR
authors.lastname: Han
authors.affiliation: Department of Pharmacology, College of Korean Medicine, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
authors.forename: Phil-Dong
authors.initials: PD
authors.lastname: Moon
authors.affiliation: Department of Pharmacology, College of Korean Medicine, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Republic of Korea. Electronic address: hmkim@khu.ac.kr.
authors.forename: Hyung-Min
authors.initials: HM
authors.lastname: Kim
authors.affiliation: Biochip Research Center and Inflammatory Disease Research Center, Hoseo University, 165, Sechul-ri, Baebang-myun, Asan, Chungnam 336-795, Republic of Korea. Electronic address: hjjeong@hoseo.edu.
authors.forename: Hyun-Ja
authors.initials: HJ
authors.lastname: Jeong
mesh_terms: D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D061207:Calcium Ionophores / Q000494:pharmacology; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism*; D003876:Dermatitis, Atopic / Q000188:drug therapy* / Q000378:metabolism*; D004139:Dinitrofluorobenzene / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects*; D006801:Humans; D008297:Male; D008407:Mast Cells / Q000187:drug effects; D051379:Mice; D011799:Quinazolines / Q000494:pharmacology* / Q000627:therapeutic use; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D013154:Spleen / Q000187:drug effects / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D061207:Calcium Ionophores; D016207:Cytokines; D011799:Quinazolines; C046243:tryptanthrine; D000001:Calcimycin; D004139:Dinitrofluorobenzene; D013755:Tetradecanoylphorbol Acetate; D000094632:Thymic Stromal Lymphopoietin
keywords: Atopic dermatitis; Caspase-1; Mast cell; TSLP; Tryptanthrin