title: A possible role for CD26/DPPIV enzyme activity in the regulation of psoriatic pruritus.
abstract: BACKGROUND
  Psoriasis (PSO) is one of the most common chronic inflammatory skin diseases, and pruritus affects approximately 60-90% of patients with PSO. However, the pathogenesis of pruritus in PSO remains unclear. Dipeptidyl peptidase IV (DPPIV) enzyme activity is involved in the regulation of peptide hormones, chemokines and neurotransmitters.
  
  
  OBJECTIVE
  Our aim is to evaluate for a potential association between DPPIV and an increased risk of pruritus, and to identify possible underlying treatment targets in affected patients.
  
  
  METHODS
  Utilizing clinical serum samples of PSO patients and in vivo experimental pruritus models, we evaluated for a potential association between DPPIV and an increased risk for pruritus, and attempted to identify possible underlying treatment targets in pruritus of PSO.
  
  
  RESULTS
  We first showed that levels of DPPIV enzyme activity in sera of patients with PSO were significantly increased compared to those of healthy controls. We next evaluated levels of substance-P (SP), which is a neurotransmitter for pruritus and a substrate for DPPIV enzyme. Truncated form SP cleaved by DPPIV was significantly increased in sera of PSO. In an in vivo pruritus model induced by SP, scratching was decreased by treatment with a DPPIV inhibitor. Moreover, DPPIV-knockout mice showed attenuation of scratching induced by SP. Finally, scratching was decreased following the administration of a DPPIV inhibitor in an imiquimod-induced PSO model. On the other hand, scratching induced by imiquimod was increased in DPPIV overexpressing-mice.
  
  
  CONCLUSIONS
  These results suggest that inhibition of DPPIV enzyme activity regulates pruritus in PSO.
authors.affiliation: Department of Therapy Development and Innovation for Immune Disorders and Cancers, Graduate School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan; Institute for Environmental and Gender Specific Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Tomioka, Urayasu, Chiba 279-0021, Japan.
authors.forename: Eriko
authors.initials: E
authors.lastname: Komiya
authors.affiliation: Department of Therapy Development and Innovation for Immune Disorders and Cancers, Graduate School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Hatano
authors.affiliation: Department of Therapy Development and Innovation for Immune Disorders and Cancers, Graduate School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
authors.forename: Haruna
authors.initials: H
authors.lastname: Otsuka
authors.affiliation: Department of Therapy Development and Innovation for Immune Disorders and Cancers, Graduate School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan; Graduate School of Health and Sports Science, Juntendo University, 1-1 Hiragagakuendai, Inzai, Chiba 270-1695, Japan.
authors.forename: Takumi
authors.initials: T
authors.lastname: Itoh
authors.affiliation: Department of Therapy Development and Innovation for Immune Disorders and Cancers, Graduate School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
authors.forename: Hiroto
authors.initials: H
authors.lastname: Yamazaki
authors.affiliation: Department of Pathology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan; Department of Pathology Saitama Medical University, 38 Morohongo, Moroyama-cho, Iruma-gun, Saitama 350-0459, Japan.
authors.forename: Taketo
authors.initials: T
authors.lastname: Yamada
authors.affiliation: Division of Hematology/Oncology, University of Florida, 1600 SW Archer Road- Box 100278, Room MSB M410A, Gainesville, FL 32610, USA.
authors.forename: Nam H
authors.initials: NH
authors.lastname: Dang
authors.affiliation: Institute for Environmental and Gender Specific Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Tomioka, Urayasu, Chiba 279-0021, Japan.
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Tominaga
authors.affiliation: Department of Dermatology, Juntendo University Urayasu Hospital, 2-1-1 Tomioka, Urayasu, Chiba 279-0021, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Suga
authors.affiliation: Department of Dermatology, Juntendo University Urayasu Hospital, 2-1-1 Tomioka, Urayasu, Chiba 279-0021, Japan.
authors.forename: Utako
authors.initials: U
authors.lastname: Kimura
authors.affiliation: Institute for Environmental and Gender Specific Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Tomioka, Urayasu, Chiba 279-0021, Japan; Department of Dermatology, Juntendo University Urayasu Hospital, 2-1-1 Tomioka, Urayasu, Chiba 279-0021, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Takamori
authors.affiliation: Department of Therapy Development and Innovation for Immune Disorders and Cancers, Graduate School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
authors.forename: Chikao
authors.initials: C
authors.lastname: Morimoto
authors.affiliation: Department of Therapy Development and Innovation for Immune Disorders and Cancers, Graduate School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. Electronic address: kohnuma@juntendo.ac.jp.
authors.forename: Kei
authors.initials: K
authors.lastname: Ohnuma
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000982:Antipruritics / Q000494:pharmacology; D001522:Behavior, Animal; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D018819:Dipeptidyl Peptidase 4 / Q000097:blood* / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D010641:Phenotype; D011537:Pruritus / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy / Q000201:enzymology*; D011565:Psoriasis / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy / Q000201:enzymology*; D013373:Substance P / Q000097:blood; D013997:Time Factors; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D000982:Antipruritics; D015415:Biomarkers; D054873:Dipeptidyl-Peptidase IV Inhibitors; D013373:Substance P; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4; C545245:Dpp4 protein, mouse
keywords: CD26/DPPIV; Pruritus; Psoriasis; Substance P