RT Journal Article
SR Electronic
T1 An Oral Drug Delivery System Targeting Immune-Regulating Cells Ameliorates Mucosal Injury in Trinitrobenzene Sulfonic Acid-Induced Colitis
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 1122
OP 1128
VO 297
IS 3
A1 Hiroshi Nakase
A1 Kazuichi Okazaki
A1 Yasuhiko Tabata
A1 Suguru Uose
A1 Masaya Ohana
A1 Kazushige Uchida
A1 Toshiki Nishi
A1 Andra's Debreceni
A1 Toshiyuki Itoh
A1 Chiharu Kawanami
A1 Masao Iwano
A1 Yoshito Ikada
A1 Tsutomu Chiba
YR 2001
UL http://jpet.aspetjournals.org/content/297/3/1122.abstract
AB Control of immune-regulating cells in the colonic mucosa is important in the treatment of patients with inflammatory bowel disease (IBD). The aim of study was to examine the therapeutic effect of dexamethasone (DX) microspheres on 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats, a model for human Crohn's disease. DX microspheres and DX alone were administered orally to rats with TNBS-induced colitis. The macroscopic score, histological score, myeloperoxidase (MPO) activity, nitric oxide (NO) production, and gene expressions of proinflammatory cytokines, cyclooxygenase (COX)-1, and COX-2 in the colonic tissue were determined. Proliferating cell nuclear antigen (PCNA) staining and expression of nuclear transcription factor (NF)-κB in colonic tissues were also investigated. Macroscopic score, histological score, MPO activity, and NO production in rats treated with DX microspheres were significantly lower than in those treated with DX alone. The gene expression of proinflammatory cytokines and COX-2 in rats treated with DX microspheres was down-regulated, compared with that in rats treated with DX alone. The number of PCNA-positive cells in the DX microsphere group was larger than in the group treated with DX alone. DX microspheres suppressed NF-κB activation in TNBS-induced colitis more strongly than DX alone. Oral administration of DX microspheres appears to ameliorate mucosal injury in TNBS-induced colitis. This drug delivery system could be an ideal therapy for human IBD. The American Society for Pharmacology and Experimental Therapeutics