title: Curcumin inhibits epigen and amphiregulin upregulated by 2,4,6-trinitrochlorobenzene associated with attenuation of skin swelling.
abstract: OBJECTIVE
  Contact dermatitis model involving repeated application of hapten is used as a tool to assess dermatitis, as characterized by thickening. Involvement of cell proliferation, elicited by repeated hapten-stimulation, in this swelling has been unclear. Curcumin is reported to reduce inflammation. We examined involvement of cell proliferation and the role of extracellular regulated kinase (ERK) in 2,4,6-trinitrochlorobenzene (TNCB) challenge-induced ear swelling. We also examined the effects of curcumin in this model.
  
  
  METHODS
  Mice were sensitized with TNCB to the abdominal skin. Then, they were challenged with TNCB to the ear three times. The ERK activation inhibitor U0126 or curcumin was applied 30 min before each TNCB challenge.
  
  
  RESULTS
  TNCB challenge-induced increased epidermal cell number and dermal thickening. Gene expressions of epithelial mitogen (EPGN), amphiregulin (AREG) and heparin-binding-epidermal growth factor (HB-EGF) were increased in the ears after the last TNCB challenge. Ki-67 immunoreactivity was increased in the dermis in TNCB-challenged ears. TNCB-induced swelling was inhibited by U0126 and curcumin. Curcumin also attenuated TNCB-induced ERK phosphorylation and expression of EPGN and AREG genes.
  
  
  CONCLUSIONS
  Ear swelling induced by TNCB challenge might be mediated, in part, by the EPGN- and AREG-ERK proliferation pathway and was inhibited by curcumin.
authors.affiliation: Division of Pharmacy Professional Development and Research, Department of Analytical Pathophysiology, School of Pharmacy, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo, 142-8501, Japan. sakai@hoshi.ac.jp.
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Sakai
authors.affiliation: Division of Pharmacy Professional Development and Research, Department of Analytical Pathophysiology, School of Pharmacy, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo, 142-8501, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Sato
authors.affiliation: Division of Pharmacy Professional Development and Research, Department of Analytical Pathophysiology, School of Pharmacy, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo, 142-8501, Japan.
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Sato
authors.affiliation: Division of Pharmacy Professional Development and Research, Department of Analytical Pathophysiology, School of Pharmacy, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo, 142-8501, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kai
authors.affiliation: Department of Pharmacology, School of Pharmacy, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo, 142-8501, Japan.
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Mandokoro
authors.affiliation: Division of Pathological Sciences, Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Yamashina, Kyoto, 607-8414, Japan.
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Matsumoto
authors.affiliation: Division of Pathological Sciences, Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Yamashina, Kyoto, 607-8414, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Kato
authors.affiliation: Division of Pharmacy Professional Development and Research, Department of Analytical Pathophysiology, School of Pharmacy, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo, 142-8501, Japan.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Yumoto
authors.affiliation: Department of Pharmacology, School of Pharmacy, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo, 142-8501, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Narita
authors.affiliation: Department of Physiology and Molecular Sciences, School of Pharmacy, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo, 142-8501, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Chiba
mesh_terms: D066258:Amphiregulin / Q000378:metabolism*; D000818:Animals; D003474:Curcumin / Q000494:pharmacology*; D016207:Cytokines / Q000235:genetics; D017449:Dermatitis, Allergic Contact / Q000378:metabolism* / Q000473:pathology; D066261:Epigen / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D006241:Haptens; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D019394:Ki-67 Antigen / Q000235:genetics / Q000378:metabolism; D008807:Mice, Inbred BALB C; D010766:Phosphorylation / Q000187:drug effects; D010853:Picryl Chloride; D012867:Skin / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D066258:Amphiregulin; C587849:Areg protein, mouse; D016207:Cytokines; C587855:Epgn protein, mouse; D066261:Epigen; D006241:Haptens; D036341:Intercellular Signaling Peptides and Proteins; D019394:Ki-67 Antigen; D048049:Extracellular Signal-Regulated MAP Kinases; D003474:Curcumin; D010853:Picryl Chloride
keywords: Contact dermatitis; Curcumin; Epidermal growth factor; Swelling