Reduced arthritis in MIF deficient mice is associated with reduced T cell activation: down-regulation of ERK MAP kinase phosphorylation

被引:40
|
作者
Santos, L. L. [1 ]
Dacumos, A. [1 ]
Yamana, J. [1 ]
Sharma, L. [2 ]
Morand, E. F. [1 ]
机构
[1] Monash Univ, Dept Med, Monash Med Ctr, Melbourne, Vic 3168, Australia
[2] Burnett Inst, Melbourne, Vic, Australia
来源
CLINICAL AND EXPERIMENTAL IMMUNOLOGY | 2008年 / 152卷 / 02期
关键词
arthritis; ERK; MIF; T cell;
D O I
10.1111/j.1365-2249.2008.03639.x
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Macrophage migration inhibitory factor (MIF) is a pleiotropic pro-inflammatory cytokine with many cellular targets in rheumatoid arthritis (RA). MIF has been reported to activate cells via mitogen-activated protein kinase and serine/threonine kinase (AKT or protein kinase B)-dependent signal transduction pathways. Its contribution to T cell activation and signalling in RA is not known. Using MIF -/- mice and a T cell-mediated model of RA, antigen-induced arthritis, we investigated the role of MIF in T cell activation and signalling. Arthritis severity was significantly reduced in MIF -/- mice compared with wildtype mice. This reduction was associated with decreased T cell activation parameters including footpad delayed type hypersensitivity, antigen-induced splenocyte proliferation and cytokine production. Splenocyte proliferation required extracellular signal-regulated kinase (ERK)1/2 phosphorylation, and decreased T cell activation in MIF -/- mice was associated with decreased phosphorylation of ERK1/2 but not AKT. Collectively, these data suggest that MIF promotes antigen-specific immune responses via regulation of ERK phosphorylation in T cells.
引用
收藏
页码:372 / 380
页数:9
相关论文
共 50 条
  • [1] DOWN-REGULATION OF THE RAS ACTIVATION PATHWAY BY MAP KINASE PHOSPHORYLATION OF SOS
    BUDAY, L
    WARNE, PH
    DOWNWARD, J
    ONCOGENE, 1995, 11 (07) : 1327 - 1331
  • [2] Reduced CREB phosphorylation after chronic lithium treatment is associated with down-regulation of CaM kinase IV in rat hippocampus
    Tardito, Daniela
    Tiraboschi, Ettore
    Kasahara, Jiro
    Racagni, Giorgio
    Popoli, Maurizio
    INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY, 2007, 10 (04): : 491 - 496
  • [3] Reduced expression of kinase-associated phosphatase in cortical dendrites of MAP2-deficient mice
    Iriuchijima, N
    Sato-Harada, R
    Takano, M
    Fujio, K
    Sato, T
    Goto, F
    Harada, A
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2005, 338 (02) : 1216 - 1221
  • [4] Down-regulation of the PI3-kinase/Akt pathway by ERK MAP kinase in growth factor signaling
    Hayashi, Hideko
    Tsuchiya, Yoshiki
    Nakayama, Kei
    Satoh, Takayuki
    Nishida, Eisuke
    GENES TO CELLS, 2008, 13 (09) : 941 - 947
  • [5] Anti-Inflammatory Action of Black Garlic through down-regulation of NF-κB activation and MAP kinase phosphorylation
    Oh, Hye Lim
    Kim, Min Jee
    You, Bo Ram
    Kim, Mee Ree
    FASEB JOURNAL, 2012, 26
  • [6] Phosphorylation and down-regulation of Bim by muscarinic cholinergic receptor activation via protein kinase C
    Styles, NA
    Zhu, WW
    Li, XH
    NEUROCHEMISTRY INTERNATIONAL, 2005, 47 (08) : 519 - 527
  • [7] Down-regulation of CXCR6 during T cell activation
    Koprak, SL
    Matheravidathu, S
    Springer, M
    Dumont, FJ
    FASEB JOURNAL, 2002, 16 (04): : A723 - A724
  • [8] DOWN-REGULATION OF HOMING RECEPTORS AFTER T-CELL ACTIVATION
    JUNG, TM
    GALLATIN, WM
    WEISSMAN, IL
    DAILEY, MO
    JOURNAL OF IMMUNOLOGY, 1988, 141 (12): : 4110 - 4117
  • [9] Impaired CREB-1 phosphorylation in antifolate-resistant cell lines with down-regulation of the reduced folate carrier gene
    Rothem, L
    Stark, M
    Assaraf, YG
    MOLECULAR PHARMACOLOGY, 2004, 66 (06) : 1536 - 1543
  • [10] Reduction in arthritis severity is associated with increased synovial p53 and reduced apoptosis in mice deficient in macrophage migration inhibitory factor (MIF).
    Leech, MT
    Xue, JR
    Lacey, D
    Morand, EF
    ARTHRITIS AND RHEUMATISM, 2002, 46 (09): : S249 - S249