%0 Journal Article
%T Colon Mucosa Exhibits Loss of Ectopic MUC5AC Expression in Patients with Ulcerative Colitis Treated with Oral Tacrolimus
%A Tsutomu Mizoshita
%A Satoshi Tanida
%A Hironobu Tsukamoto
%A Keiji Ozeki
%A Takahito Katano
%A Masahide Ebi
%A Yoshinori Mori
%A Hiromi Kataoka
%A Takeshi Kamiya
%A Takashi Joh
%J ISRN Gastroenterology
%D 2013
%R 10.1155/2013/304894
%X Background. Tacrolimus (FK506) is effective for patients with ulcerative colitis (UC). However, there are few reports on tacrolimus therapy (TT) with respect to the relationship with endoscopic and clinicopathologic findings. Methods. Thirty patients with moderate/severe active UC refractory to or dependent on corticosteroid were treated with oral tacrolimus. The expression of ectopic MUC5AC in the colon was pathologically analyzed before and at 12 weeks after TT, evaluating the Mayo score and steroid-sparing effects. Results. Both mean disease and endoscopic activity index scores were reduced at levels of statistical significance in 26 UC patients receiving more than one month of TT ( ). The dose of prednisolone was reduced by a statistically significant amount ( ), and 14 of the 26 patients (53.8%) had steroid-free status 12 weeks after TT. The decrease in ectopic MUC5AC expression in the mucous cells of the colon was significantly associated with endoscopic improvement of inflammation in the UC patients with TT ( ). Loss of ectopic MUC5AC expression was detected in all patients who had complete response. Conclusions. Tacrolimus appears to be effective for the treatment of moderate/severe UC patients. Loss of ectopic MUC5AC expression may be important for pathologic remission in the colon of UC patients. 1. Introduction Ulcerative colitis (UC) is an idiopathic, chronic, and inflammatory disorder characterized by diarrhea, rectal bleeding, abdominal pain, fever, anemia, and body weight loss [1, 2]. Corticosteroid (CS) therapy is administered to patients with UC when flare-ups occur [1, 3]. Most patients with UC initially respond to CS therapy, but about 20% of patients become steroid dependent within 1 year after CS therapy starts [4]. Steroid-free status is important for patients with UC because CSs often induce undesirable side effects such as diabetes mellitus, osteoporosis, and opportunistic infections [2, 5]. Tacrolimus (FK506) is effective for patients with UC refractory to or dependent on CS and is usually used as a rescue and bridging therapy before initiating azathioprine (AZA) or 6-mercaptopurine (6-MP) therapy [6¨C12]. Tacrolimus therapy is useful as an alternative therapy for steroid-refractory UC [13]. Tacrolimus induces inhibition of the transcription of the early activation genes encoding interleukin- (IL-) 2, tumor necrosis factor-¦Á (TNF-¦Á), and interferon-¦Ã (IFN-¦Ã) that are responsible for the development of inflammation [6, 14]. A higher initial dose of tacrolimus has been observed to ensure achievement of target levels [15]. In a
%U http://www.hindawi.com/journals/isrn.gastroenterology/2013/304894/