title: Mycophenolate Mofetil Modulates Differentiation of Th1/Th2 and the Secretion of Cytokines in an Active Crohn's Disease Mouse Model.
abstract: Mycophenolate mofetil (MMF) is an alternative immunosuppressive agent that has been reported to be effective and well tolerated for the treatment of refractory inflammatory bowel disease (IBD). The aim of this study was to investigate the therapeutic effect of MMF on intestinal injury and tissue inflammation, which were caused by Crohn's disease (CD). Here, trinitrobenzene sulfonic acid-relapsing (TNBS) colitis was induced in mice; then, we measured the differentiation of Th1/Th2 cells in mouse splenocytes by flow cytometry and the secretion of cytokines in mice with TNBS-induced colitis by real-time polymerase chain reaction and/or enzyme-linked immunosorbent assay (RT-PCR/ELISA). The results show that MMF significantly inhibited mRNA expression of pro-inflammatory cytokines IFN-γ, TNF-α, IL-12, IL-6, and IL-1β in mice with TNBS-induced colitis; however, MMF did not inhibit the expression of IL-10 mRNA. Additionally, ELISA showed that the serum levels of IFN-γ, TNF-α, IL-12, IL-6, and IL-1β were down-regulated in a TNBS model of colitis. Flow cytometric analysis showed MMF markedly reduced the percentages of Th1 and Th2 splenocytes in the CD mouse model. Mycophenolic acid (MPA) also significantly decreased the percentages of splenic Th1 and Th2 cells in vitro. Furthermore, MMF treatment not only significantly ameliorated diarrhea, and loss of body weight but also abrogated the histopathologic severity and inflammatory response of inflammatory colitis, and increased the survival rate of TNBS-induced colitic mice. These results suggest that treatment with MMF may improve experimental colitis and induce inflammatory response remission of CD by down-regulation of pro-inflammatory cytokines via modulation of the differentiation of Th1/Th2 cells.
authors.affiliation: College of Veterinary Medicine, Jilin University, China. lvqingkang@hotmail.com.
authors.forename: Qing-Kang
authors.initials: QK
authors.lastname: Lv
authors.affiliation: College of Veterinary Medicine, Jilin University, China. juxiong@jlu.edu.cn.
authors.forename: Ju-Xiong
authors.initials: JX
authors.lastname: Liu
authors.affiliation: College of Veterinary Medicine, Jilin University, China. fengerwin1@sina.com.
authors.forename: Su-Nan
authors.initials: SN
authors.lastname: Li
authors.affiliation: College of Veterinary Medicine, Jilin University, China. yjgao@jlu.edu.cn.
authors.forename: Ying-Jie
authors.initials: YJ
authors.lastname: Gao
authors.affiliation: College of Veterinary Medicine, Jilin University, China. lvyanty@jlu.edu.cn.
authors.forename: Yan
authors.initials: Y
authors.lastname: Lv
authors.affiliation: PengCheng Gastroenterology Hospital, Changchun 130062, China. xuzipeng1950@sina.com.
authors.forename: Zi-Peng
authors.initials: ZP
authors.lastname: Xu
authors.affiliation: College of Veterinary Medicine, Jilin University, China. huangbingxu123@outlook.com.
authors.forename: Bing-Xu
authors.initials: BX
authors.lastname: Huang
authors.affiliation: College of Veterinary Medicine, Jilin University, China. gladys20@sina.com.
authors.forename: Shi-Yao
authors.initials: SY
authors.lastname: Xu
authors.affiliation: College of Veterinary Medicine, Jilin University, China. yangdxaig@outlook.com.
authors.forename: Dong-Xue
authors.initials: DX
authors.lastname: Yang
authors.affiliation: College of Veterinary Medicine, Jilin University, China. zengyalong@foxmail.com.
authors.forename: Ya-Long
authors.initials: YL
authors.lastname: Zeng
authors.affiliation: College of Veterinary Medicine, Jilin University, China. liudf@jlu.edu.cn.
authors.forename: Dian-Feng
authors.initials: DF
authors.lastname: Liu
authors.affiliation: College of Veterinary Medicine, Jilin University, China. wang_wei99@jlu.edu.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects* / Q000276:immunology; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D003424:Crohn Disease / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology; D053583:Interleukin-1beta / Q000235:genetics / Q000276:immunology; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D013154:Spleen / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D058408:Th1-Th2 Balance / Q000187:drug effects; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D014302:Trinitrobenzenesulfonic Acid; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D007166:Immunosuppressive Agents; D053583:Interleukin-1beta; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; C577686:interleukin-6, mouse; D018664:Interleukin-12; D007371:Interferon-gamma; D014302:Trinitrobenzenesulfonic Acid; D009173:Mycophenolic Acid
keywords: Th1/Th2 cells; cytokine; inflammatory bowel disease; mycophenolate mofetil