Calcineurin inhibition by polaprezinc in rats with experimentally-induced colitis
| Autor: | Masatomo Mori, Shinichi Okamura, Tomohiro Kudo, Takashige Masuo, Yajing Zhang |
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| Rok vydání: | 2011 |
| Předmět: |
Male
Cell Survival T-Lymphocytes Calcineurin Inhibitors Gene Expression Pharmacology Biology Jurkat cells General Biochemistry Genetics and Molecular Biology Proinflammatory cytokine Jurkat Cells Intestinal mucosa Administration Rectal Organometallic Compounds medicine Animals Humans Intestinal Mucosa Rats Wistar General Pharmacology Toxicology and Pharmaceutics Colitis NFATC Transcription Factors Reverse Transcriptase Polymerase Chain Reaction Calcineurin Carnosine NFAT General Medicine Polaprezinc Anti-Ulcer Agents medicine.disease Rats Disease Models Animal Trinitrobenzenesulfonic Acid Zinc Compounds Cancer research Cytokines Interleukin-2 |
| Zdroj: | Life Sciences. 88:432-439 |
| ISSN: | 0024-3205 |
| Popis: | Aims 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. Main 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. Key findings 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. Significance Our results suggest that PZ can be used as an immunosuppressive agent for the treatment of colitis through its inhibitory effect on CN activity. |
| Databáze: | OpenAIRE |
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