COX-2 inhibitors ameliorate experimental autoimmune encephalomyelitis through modulating IFN-gamma and IL-10 production by inhibiting T-bet expression.
The COX-2 inhibitors Rofecoxib (Rof) and Lumiracoxib (Lum) were evaluated in experimental autoimmune encephalomyelitis (EAE), the model of multiple sclerosis (MS). Administration of Rof and Lum significantly reduced the incidence and severity of EAE, which was associated with the inhibition of MOG 35-55 lymphocyte recall response, anti-MOG 35-55 T cell responses, and modulation of cytokines production. In vitro Rof and Lum inhibited primary T cells proliferation and modulated cytokine production. These findings highlight the fact that Rof and Lum likely prevents EAE by modulating Th1/Th2 response, and suggest its utility in the treatment of MS and other autoimmune diseases.
Ni
Jia
J
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 201203, People's Republic of China.
Shu
Ying-Yi
YY
Zhu
Yi-Na
YN
Fu
Yun-Feng
YF
Tang
Wei
W
Zhong
Xiang-Gen
XG
Wang
Hui
H
Yang
Yi-Fu
YF
Ren
Jin
J
Wang
Ming-Wei
MW
Zuo
Jian-Ping
JP
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use*; D004008:Diclofenac / Q000031:analogs & derivatives / Q000627:therapeutic use; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007371:Interferon-gamma / Q000378:metabolism*; D016753:Interleukin-10 / Q000378:metabolism*; D007783:Lactones / Q000627:therapeutic use; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D013450:Sulfones / Q000627:therapeutic use; D020825:T-Box Domain Proteins / Q000378:metabolism*; D013601:T-Lymphocytes / Q000187:drug effects; D013997:Time Factors; D000098815:T-bet Transcription Factor
D052246:Cyclooxygenase 2 Inhibitors; D007783:Lactones; D013450:Sulfones; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; C116926:rofecoxib; D016753:Interleukin-10; D004008:Diclofenac; D007371:Interferon-gamma; C473384:lumiracoxib