title: Calcineurin inhibition by polaprezinc in rats with experimentally-induced colitis.
abstract: OBJECTIVE
  We investigated the therapeutic effect of polaprezinc (PZ), N-(3-aminopropionyl)-L-histidinato zinc, in rats with experimentally-induced colitis by focusing on calcineurin (CN) inhibition. CN plays a crucial role in T-cell activation and cytokine gene expression and is targeted by immunosuppressants such as cyclosporine and FK506.
  
  
  METHODS
  Colitis was induced into male Wistar rats by trinitrobenzene sulfonic acid and was treated with intrarectally administered PZ. The inflammation was assessed by the macroscopic damage score, colon wet weight, and proinflammatory mediator expression by RT-PCR analysis. Protein expression of calcineurin and the activation of its substrate, the nuclear factor of activated T cells (NFAT) transcription factor, were also studied. Calcineurin inhibition by PZ was investigated in in vitro experiments using colonic mucosa, purified calcineurin enzyme, and Jurkat T cells.
  
  
  RESULTS
  CN was activated in the colitic mucosa; PZ treatment inhibited CN activation, the expression of proinflammatory cytokines in the mucosa, and thereby ameliorated the experimental colitis in rats. In in vitro experiments, PZ inhibited CN activity, NFAT activation, interleukin-2 expression, and the growth of Jurkat T cells. In the effective concentrations, PZ did not affect cell viability.
  
  
  CONCLUSIONS
  Our results suggest that PZ can be used as an immunosuppressive agent for the treatment of colitis through its inhibitory effect on CN activity.
authors.affiliation: Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan.
authors.forename: Yajing
authors.initials: Y
authors.lastname: Zhang
authors.forename: Shinichi
authors.initials: S
authors.lastname: Okamura
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kudo
authors.forename: Takashige
authors.initials: T
authors.lastname: Masuo
authors.forename: Masatomo
authors.initials: M
authors.lastname: Mori
mesh_terms: D000285:Administration, Rectal; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D019703:Calcineurin / Q000378:metabolism; D065095:Calcineurin Inhibitors; D002336:Carnosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects / Q000201:enzymology; D019169:Jurkat Cells; D008297:Male; D050778:NFATC Transcription Factors / Q000378:metabolism; D009942:Organometallic Compounds / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D014302:Trinitrobenzenesulfonic Acid / Q000633:toxicity; D017967:Zinc Compounds / Q000494:pharmacology
chemical_list: D000897:Anti-Ulcer Agents; D065095:Calcineurin Inhibitors; D016207:Cytokines; D007376:Interleukin-2; D050778:NFATC Transcription Factors; D009942:Organometallic Compounds; D017967:Zinc Compounds; C061957:polaprezinc; D002336:Carnosine; D014302:Trinitrobenzenesulfonic Acid; D019703:Calcineurin