PMID- 21909699
OWN - NLM
STAT- MEDLINE
DCOM- 20120217
LR  - 20211020
IS  - 1434-9949 (Electronic)
IS  - 0770-3198 (Linking)
VI  - 30
IP  - 11
DP  - 2011 Nov
TI  - Inhibition of MAP kinase in synovium by treatment with tocilizumab in rheumatoid 
      arthritis.
PG  - 1407-13
LID - 10.1007/s10067-011-1833-z [doi]
AB  - To investigate the histological changes of mitogen-activated protein kinase 
      (MAPK) in synovium with tocilizumab in rheumatoid arthritis (RA), synovial tissue 
      samples were assessed from ten methotrexate (MTX)-treated RA patients for control 
      and ten tocilizumab with MTX-treated RA patients. The synovium was observed using 
      hematoxylin and eosin (H&E) stain and analyzed immunohistochemically for the 
      expression of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), matrix 
      metalloproteinase-3 (MMP-3), CD4 (T cell), CD20 (B cell), CD68 (macrophage), 
      vascular endothelial growth factor (VEGF), CD29 (beta-1 integrin), phospho-p38 MAPK 
      (Tyr180/Tyr182), phospho-p44/42 MAPK [extracellular signal-regulated kinase (ERK) 
      1/ERK2], and phospho-c-Jun N-terminal kinase (JNK). H&E staining showed that 
      there is a significant difference of cell proliferation; however, there is no 
      change of hypervascularity in the synovium between both groups. An 
      immunohistochemical examination showed that the decrease of CD29 (beta-1 integrin) 
      and JNK was found significant, while ERK was increased in the tocilizumab group. 
      CD20, B-lymphocyte, was decreased in the tocilizumab group compared with the MTX 
      group significantly. IL-6 was completely blocked in the patients who received 
      tocilizumab. TNF-alpha was similarly expressed in the interstitial cells of synovium 
      of patients in both groups. MMP-3 and CD68 were similarly expressed on the 
      surface of synovium. VEGF was less expressed in both groups. These findings 
      indicate that the inhibition of CD20, CD29, and JNK in MAPK may be involved in 
      the efficacy of tocilizumab compared with MTX treatment in RA.
FAU - Kanbe, Katsuaki
AU  - Kanbe K
AD  - Department of Orthopaedic Surgery, Tokyo Women's Medical University, Medical 
      Center East, 2-1-10 Nishiogu, Arakawa, Tokyo, Japan. kanbeor@dnh.twmu.ac.jp
FAU - Chen, Qian
AU  - Chen Q
FAU - Nakamura, Atsushi
AU  - Nakamura A
FAU - Hobo, Kaori
AU  - Hobo K
LA  - eng
PT  - Journal Article
DEP - 20110910
PL  - Germany
TA  - Clin Rheumatol
JT  - Clinical rheumatology
JID - 8211469
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Antigens, CD)
RN  - 0 (Antirheumatic Agents)
RN  - 0 (Cytokines)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
RN  - I031V2H011 (tocilizumab)
RN  - YL5FZ2Y5U1 (Methotrexate)
SB  - IM
MH  - Aged
MH  - Antibodies, Monoclonal, Humanized/pharmacology/*therapeutic use
MH  - Antigens, CD/metabolism
MH  - Antirheumatic Agents/pharmacology/*therapeutic use
MH  - Arthritis, Rheumatoid/*drug therapy/metabolism/pathology
MH  - Cytokines/metabolism
MH  - Female
MH  - Humans
MH  - JNK Mitogen-Activated Protein Kinases/metabolism
MH  - MAP Kinase Signaling System/*drug effects
MH  - Male
MH  - Matrix Metalloproteinase 3/metabolism
MH  - Methotrexate/therapeutic use
MH  - Middle Aged
MH  - Synovial Membrane/*drug effects/metabolism/pathology
MH  - Vascular Endothelial Growth Factor A/metabolism
EDAT- 2011/09/13 06:00
MHDA- 2012/02/18 06:00
CRDT- 2011/09/13 06:00
PHST- 2011/01/27 00:00 [received]
PHST- 2011/08/15 00:00 [accepted]
PHST- 2011/07/24 00:00 [revised]
PHST- 2011/09/13 06:00 [entrez]
PHST- 2011/09/13 06:00 [pubmed]
PHST- 2012/02/18 06:00 [medline]
AID - 10.1007/s10067-011-1833-z [doi]
PST - ppublish
SO  - Clin Rheumatol. 2011 Nov;30(11):1407-13. doi: 10.1007/s10067-011-1833-z. Epub 
      2011 Sep 10.