PMID- 21679443
OWN - NLM
STAT- MEDLINE
DCOM- 20120313
LR  - 20240507
IS  - 1478-6362 (Electronic)
IS  - 1478-6354 (Print)
IS  - 1478-6354 (Linking)
VI  - 13
IP  - 3
DP  - 2011 Jun 16
TI  - Abnormal networks of immune response-related molecules in bone marrow cells from 
      patients with rheumatoid arthritis as revealed by DNA microarray analysis.
PG  - R89
LID - 10.1186/ar3364 [doi]
AB  - INTRODUCTION: Rheumatoid arthritis (RA) is a systemic autoimmune disease 
      characterized by chronic synovitis that progresses to destruction of cartilage 
      and bone. Bone marrow (BM) cells have been shown to contribute to this 
      pathogenesis. In this study, we compared differentially expressed molecules in BM 
      cells from RA and osteoarthritis (OA) patients and analyzed abnormal regulatory 
      networks to identify the role of BM cells in RA. METHODS: Gene expression 
      profiles (GEPs) in BM-derived mononuclear cells from 9 RA and 10 OA patients were 
      obtained by DNA microarray. Up- and down-regulated genes were identified by 
      comparing the GEPs from the two patient groups. Bioinformatics was performed by 
      Expression Analysis Systemic Explorer (EASE) 2.0 based on gene ontology, followed 
      by network pathway analysis with Ingenuity Pathways Analysis (IPA) 7.5. RESULTS: 
      The BM mononuclear cells showed 764 up-regulated and 1,910 down-regulated genes 
      in RA patients relative to the OA group. EASE revealed that the gene category 
      response to external stimulus, which included the gene category immune response, 
      was overrepresented by the up-regulated genes. So too were the gene categories 
      signal transduction and phosphate metabolism. Down-regulated genes were 
      dominantly classified in three gene categories: cell proliferation, which 
      included mitotic cell cycle, DNA replication and chromosome cycle, and DNA 
      metabolism. Most genes in these categories overlapped with each other. IPA 
      analysis showed that the up-regulated genes in immune response were highly 
      relevant to the antigen presentation pathway and to interferon signaling. The 
      major histocompatibility complex (MHC) class I molecules, human leukocyte antigen 
      (HLA)-E, HLA-F, and HLA-G, tapasin (TAP) and TAP binding protein, both of which 
      are involved in peptide antigen binding and presentation via MHC class I 
      molecules, are depicted in the immune response molecule networks. Interferon 
      gamma and interleukin 8 were overexpressed and found to play central roles in 
      these networks. CONCLUSIONS: Abnormal regulatory networks in the immune response 
      and cell cycle categories were identified in BM mononuclear cells from RA 
      patients, indicating that the BM is pathologically involved in RA.
FAU - Lee, Hooi-Ming
AU  - Lee HM
AD  - Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamada-Oka, Suita, 
      Osaka 565-0871, Japan.
FAU - Sugino, Hidehiko
AU  - Sugino H
FAU - Aoki, Chieko
AU  - Aoki C
FAU - Shimaoka, Yasunori
AU  - Shimaoka Y
FAU - Suzuki, Ryuji
AU  - Suzuki R
FAU - Ochi, Kensuke
AU  - Ochi K
FAU - Ochi, Takahiro
AU  - Ochi T
FAU - Nishimoto, Norihiro
AU  - Nishimoto N
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110616
PL  - England
TA  - Arthritis Res Ther
JT  - Arthritis research & therapy
JID - 101154438
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Arthritis, Rheumatoid/*genetics/*immunology
MH  - Bone Marrow Cells/cytology/*immunology
MH  - Down-Regulation/genetics/immunology
MH  - *Gene Expression Profiling
MH  - Gene Expression Regulation/immunology
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Mitosis/genetics/immunology
MH  - *Oligonucleotide Array Sequence Analysis
MH  - Osteoarthritis/genetics/immunology
MH  - Up-Regulation/genetics/immunology
PMC - PMC3218904
EDAT- 2011/06/18 06:00
MHDA- 2012/03/14 06:00
PMCR- 2011/06/16
CRDT- 2011/06/18 06:00
PHST- 2011/03/03 00:00 [received]
PHST- 2011/04/20 00:00 [revised]
PHST- 2011/06/16 00:00 [accepted]
PHST- 2011/06/18 06:00 [entrez]
PHST- 2011/06/18 06:00 [pubmed]
PHST- 2012/03/14 06:00 [medline]
PHST- 2011/06/16 00:00 [pmc-release]
AID - ar3364 [pii]
AID - 10.1186/ar3364 [doi]
PST - epublish
SO  - Arthritis Res Ther. 2011 Jun 16;13(3):R89. doi: 10.1186/ar3364.