PMID- 28405735 OWN - NLM STAT- MEDLINE DCOM- 20180416 LR - 20181113 IS - 1420-908X (Electronic) IS - 1023-3830 (Linking) VI - 66 IP - 8 DP - 2017 Aug TI - Curcumin inhibits epigen and amphiregulin upregulated by 2,4,6-trinitrochlorobenzene associated with attenuation of skin swelling. PG - 663-678 LID - 10.1007/s00011-017-1048-0 [doi] AB - OBJECTIVES: 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. CONCLUSION: Ear swelling induced by TNCB challenge might be mediated, in part, by the EPGN- and AREG-ERK proliferation pathway and was inhibited by curcumin. FAU - Sakai, Hiroyasu AU - Sakai H AD - 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. FAU - Sato, Ken AU - Sato K AD - 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. FAU - Sato, Fumiaki AU - Sato F AD - 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. FAU - Kai, Yuki AU - Kai Y AD - 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. FAU - Mandokoro, Kazutaka AU - Mandokoro K AD - Department of Pharmacology, School of Pharmacy, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo, 142-8501, Japan. FAU - Matsumoto, Kenjiro AU - Matsumoto K AD - Division of Pathological Sciences, Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Yamashina, Kyoto, 607-8414, Japan. FAU - Kato, Shinichi AU - Kato S AD - Division of Pathological Sciences, Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Yamashina, Kyoto, 607-8414, Japan. FAU - Yumoto, Tetsuro AU - Yumoto T AD - 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. FAU - Narita, Minoru AU - Narita M AD - Department of Pharmacology, School of Pharmacy, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo, 142-8501, Japan. FAU - Chiba, Yoshihiko AU - Chiba Y AD - Department of Physiology and Molecular Sciences, School of Pharmacy, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo, 142-8501, Japan. LA - eng PT - Journal Article DEP - 20170412 PL - Switzerland TA - Inflamm Res JT - Inflammation research : official journal of the European Histamine Research Society ... [et al.] JID - 9508160 RN - 0 (Amphiregulin) RN - 0 (Areg protein, mouse) RN - 0 (Cytokines) RN - 0 (Epgn protein, mouse) RN - 0 (Epigen) RN - 0 (Haptens) RN - 0 (Intercellular Signaling Peptides and Proteins) RN - 0 (Ki-67 Antigen) RN - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases) RN - IT942ZTH98 (Curcumin) RN - Z4ZG7O5SZ9 (Picryl Chloride) SB - IM MH - Amphiregulin/*metabolism MH - Animals MH - Curcumin/*pharmacology MH - Cytokines/genetics MH - Dermatitis, Allergic Contact/*metabolism/pathology MH - Epigen/*metabolism MH - Extracellular Signal-Regulated MAP Kinases/metabolism MH - Female MH - Haptens MH - Intercellular Signaling Peptides and Proteins/genetics MH - Ki-67 Antigen/genetics/metabolism MH - Mice, Inbred BALB C MH - Phosphorylation/drug effects MH - Picryl Chloride MH - Skin/drug effects/metabolism/pathology MH - Up-Regulation/drug effects OTO - NOTNLM OT - Contact dermatitis OT - Curcumin OT - Epidermal growth factor OT - Swelling EDAT- 2017/04/14 06:00 MHDA- 2018/04/17 06:00 CRDT- 2017/04/14 06:00 PHST- 2017/03/07 00:00 [received] PHST- 2017/04/06 00:00 [accepted] PHST- 2017/04/04 00:00 [revised] PHST- 2017/04/14 06:00 [pubmed] PHST- 2018/04/17 06:00 [medline] PHST- 2017/04/14 06:00 [entrez] AID - 10.1007/s00011-017-1048-0 [pii] AID - 10.1007/s00011-017-1048-0 [doi] PST - ppublish SO - Inflamm Res. 2017 Aug;66(8):663-678. doi: 10.1007/s00011-017-1048-0. Epub 2017 Apr 12.