An oral drug delivery system targeting immune-regulating cells ameliorates mucosal injury in trinitrobenzene sulfonic acid-induced colitis.
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)-kappaB 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-kappaB 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.
Nakase
H
H
Division of Gastroenterology and Endoscopic Medicine, and Institute for Frontier Medical Science, Kyoto University, Kyoto, Japan.
Okazaki
K
K
Tabata
Y
Y
Uose
S
S
Ohana
M
M
Uchida
K
K
Nishi
T
T
Debreceni
A
A
Itoh
T
T
Kawanami
C
C
Iwano
M
M
Ikada
Y
Y
Chiba
T
T
D000284:Administration, Oral; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D051545:Cyclooxygenase 1; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D003907:Dexamethasone / Q000008:administration & dosage*; D004195:Disease Models, Animal; D016503:Drug Delivery Systems / Q000379:methods*; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D008565:Membrane Proteins; D008863:Microspheres; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D009569:Nitric Oxide / Q000096:biosynthesis; D009195:Peroxidase / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D016896:Treatment Outcome; D014302:Trinitrobenzenesulfonic Acid
D016207:Cytokines; D007527:Isoenzymes; D008565:Membrane Proteins; D016328:NF-kappa B; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D009569:Nitric Oxide; D003907:Dexamethasone; D014302:Trinitrobenzenesulfonic Acid; D009195:Peroxidase; D051545:Cyclooxygenase 1; D011451:Prostaglandin-Endoperoxide Synthases; C496513:Ptgs1 protein, rat