PMID- 23334372
OWN - NLM
STAT- MEDLINE
DCOM- 20141013
LR  - 20211021
IS  - 1437-160X (Electronic)
IS  - 0172-8172 (Linking)
VI  - 34
IP  - 1
DP  - 2014 Jan
TI  - Inhibition of JNK in synovium by treatment with golimumab in rheumatoid 
      arthritis.
PG  - 125-30
LID - 10.1007/s00296-012-2626-7 [doi]
AB  - The aim of this study was to investigate immunohistological changes in 
      mitogen-activated protein kinases (MAPKs) in the synovium following treatment 
      with golimumab, compared with methotrexate (MTX). We assessed synovial tissues 
      for 13 different molecules to detect cytokine levels histologically from 10 
      methotrexate (MTX)-treated rheumatoid arthritis (RA) patients as controls and 10 
      golimumab plus MTX-treated RA patients. Synovium samples from both groups were 
      assessed by hematoxylin and eosin (HE) staining and analyzed for expression of 
      tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), matrix metalloproteinase-3 
      (MMP-3), CD4 (T cells), CD8 (T cells), CD20 (B cells), CD68 (macrophages), 
      receptor activator of nuclear (kappa) B ligand (RANKL), bromodeoxyuridine (BrdU), 
      CD29 (beta-1 integrin), phospho-p38 MAPK (Tyr180/Tyr182), phospho-p44/42 MAPK 
      (ERK1/ERK2), and phospho-c-Jun N-terminal kinase (JNK), by an immunohistological 
      examination. HE staining showed that there was a significant decrease in cell 
      proliferation in the synovium in RA patients who received golimumab compared with 
      the controls. TNF-alpha, IL-6, MMP3, BrdU, p38, and ERK were not seen at significant 
      levels in either group. On the other hand, CD4, CD8, CD20, CD29, CD68, RANKL, and 
      JNK were significantly decreased in the golimumab group compared with the 
      control. Based on a histological analysis of the synovium, it appears that the 
      efficacy of the treatment with golimumab may involve the inhibition of cell 
      proliferation, with decreases in T cells, B cells, macrophages, beta-1 integrin, 
      RANKL, and JNK in the synovium, 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, 116-8567, Japan, 
      kanbeor@dnh.twmu.ac.jp.
FAU - Chiba, Junji
AU  - Chiba J
FAU - Nakamura, Atsushi
AU  - Nakamura A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130119
PL  - Germany
TA  - Rheumatol Int
JT  - Rheumatology international
JID - 8206885
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antirheumatic Agents)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 91X1KLU43E (golimumab)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - YL5FZ2Y5U1 (Methotrexate)
SB  - IM
MH  - Aged
MH  - Antibodies, Monoclonal/*therapeutic use
MH  - Antirheumatic Agents/*therapeutic use
MH  - Arthritis, Rheumatoid/*drug therapy/enzymology/immunology/pathology
MH  - Case-Control Studies
MH  - Enzyme Activation
MH  - Female
MH  - Humans
MH  - Inflammation Mediators/metabolism
MH  - JNK Mitogen-Activated Protein Kinases/*antagonists & inhibitors/metabolism
MH  - Male
MH  - Methotrexate/therapeutic use
MH  - Middle Aged
MH  - Phosphorylation
MH  - Protein Kinase Inhibitors/*therapeutic use
MH  - Signal Transduction/drug effects
MH  - Synovial Membrane/*drug effects/enzymology/pathology
MH  - Treatment Outcome
EDAT- 2013/01/22 06:00
MHDA- 2014/10/14 06:00
CRDT- 2013/01/22 06:00
PHST- 2012/06/14 00:00 [received]
PHST- 2012/12/09 00:00 [accepted]
PHST- 2013/01/22 06:00 [entrez]
PHST- 2013/01/22 06:00 [pubmed]
PHST- 2014/10/14 06:00 [medline]
AID - 10.1007/s00296-012-2626-7 [doi]
PST - ppublish
SO  - Rheumatol Int. 2014 Jan;34(1):125-30. doi: 10.1007/s00296-012-2626-7. Epub 2013 
      Jan 19.