title: A novel compound 2-(4-{2-[(phenylthio)acetyl]carbonohydrazonoyl}phenoxy)acetamide downregulates TSLP through blocking of caspase-1/NF-κB pathways.
abstract: Thymic stromal lymphopoietin (TSLP) is regarded as the main factor responsible for the pathogenesis of allergic disorders such as atopic dermatitis, chronic obstructive pulmonary diseases, and allergic rhinitis. As part of our continuing search for novel anti-inflammatory compounds, 2-(4-{2-[(phenylthio)acetyl]carbonohydrazonoyl}phenoxy)acetamide (PA) was analyzed. In the present study, we examined how PA regulates the mRNA expression and production of TSLP in the human mast cell line, HMC-1 cells. Computer-aided docking simulation, enzyme-linked immunosorbent assay, quantitative polymerase chain reaction, caspase-1 assay, and Western blotting were used to investigate the effects of PA. PA decreased the mRNA expression and production of TSLP in HMC-1 cells. PA (1μM) inhibited the TSLP production up to 87.710±5.201%. PA also improved the activation and phosphorylation of nuclear factor-κB as well as the degradation and phosphorylation of IκBα. Caspase-1 activation was up-regulated in activated HMC-1 cells, whereas caspase-1 activation was down-regulated by PA. Finally, PA inhibited ear swelling response induced by phorbol myristate acetate in mice. These results indicate that PA would be effective to treat inflammatory and atopic disorders through the down-regulations 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: 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.
authors.forename: Na-Ra
authors.initials: NR
authors.lastname: Han
authors.affiliation: Department of Pharmacology, Graduate School, Kyung Hee University, Seoul, 130-701, Republic of Korea.
authors.forename: Ka-Jung
authors.initials: KJ
authors.lastname: Ryu
authors.affiliation: Department of Pharmacology, Graduate School, Kyung Hee University, Seoul, 130-701, Republic of Korea.
authors.forename: Sang-Woo
authors.initials: SW
authors.lastname: Kang
authors.affiliation: Department of Pharmacology, Graduate School, Kyung Hee University, Seoul, 130-701, Republic of Korea.
authors.forename: Ji-Hyun
authors.initials: JH
authors.lastname: Go
authors.affiliation: Department of Pharmaceutical engineering and Inflammatory Disease Research Center, Hoseo University, Asan, Chungnam 336-795, Republic of Korea.
authors.forename: Jae-Bum
authors.initials: JB
authors.lastname: Jang
authors.affiliation: Department of Food Technology and Inflammatory Disease Research Center, Hoseo University, Asan, Chungnam 336-795 Republic of Korea.
authors.forename: Youngjin
authors.initials: Y
authors.lastname: Choi
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: Department of Food Technology and Inflammatory Disease Research Center, Hoseo University, Asan, Chungnam 336-795 Republic of Korea. Electronic address: hjjeong@hoseo.edu.
authors.forename: Hyun-Ja
authors.initials: HJ
authors.lastname: Jeong
mesh_terms: D000081:Acetamides / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D018926:Anti-Allergic Agents / Q000138:chemical synthesis / Q000627:therapeutic use*; D020170:Caspase 1 / Q000378:metabolism; D002460:Cell Line; D019295:Computational Biology / Q000379:methods; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D003876:Dermatitis, Atopic / Q000188:drug therapy*; D004195:Disease Models, Animal; D055808:Drug Discovery; D006801:Humans; D006835:Hydrazones / Q000138:chemical synthesis / Q000494:pharmacology*; D008407:Mast Cells / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D008815:Mice, Inbred Strains; D016328:NF-kappa B / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D054852:Small Molecule Libraries; D013755:Tetradecanoylphorbol Acetate; D000094632:Thymic Stromal Lymphopoietin
chemical_list: C000616812:2-(4-(2-((phenylthio)acetyl)carbonohydrazonoyl)phenoxy)acetamide; D000081:Acetamides; D018926:Anti-Allergic Agents; D016207:Cytokines; D006835:Hydrazones; D016328:NF-kappa B; D054852:Small Molecule Libraries; D020170:Caspase 1; D013755:Tetradecanoylphorbol Acetate; D000094632:Thymic Stromal Lymphopoietin
keywords: 2-(4-{2-[(Phenylthio)acetyl]carbonohydrazonoyl}phenoxy)acetamide; Caspase-1; Nuclear factor-κB; Thymic stromal lyemphopoietin