PMID- 18439312
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20110714
LR  - 20211020
IS  - 1476-9255 (Electronic)
IS  - 1476-9255 (Linking)
VI  - 5
DP  - 2008 Apr 27
TI  - Proinflammatory role of amphiregulin, an epidermal growth factor family member 
      whose expression is augmented in rheumatoid arthritis patients.
PG  - 5
LID - 10.1186/1476-9255-5-5 [doi]
AB  - BACKGROUND: The epidermal growth factor (EGF) and EGF receptor (EGFR) families 
      play important roles in the hyperplastic growth of several tissues as well as 
      tumor growth. Since synovial hyperplasia in rheumatoid arthritis (RA) resembles a 
      tumor, involvement of the EGF/EGFR families in RA pathology has been implied. 
      Although several reports have suggested that ErbB2 is the most important member 
      of the EGFR family for the synovitis in RA, it remains unclear which members of 
      the EGF family are involved. To clarify the EGF-like growth factors involved in 
      the pathology of RA, we investigated the expression levels of seven major 
      EGF-like growth factors in RA patients compared with those in osteoarthritis (OA) 
      patients and healthy control subjects. METHODS: The expression levels of seven 
      EGF-like growth factors and four EGFR-like receptors were measured in mononuclear 
      cells isolated from bone marrow and venous blood, as well as in synovial tissues, 
      using quantitative RT-PCR. Further evidence of gene expression was obtained by 
      ELISAs. The proinflammatory roles were assessed by the growth-promoting and 
      cytokine-inducing effects of the corresponding recombinant proteins on cultured 
      fibroblast-like synoviocytes (FLS). RESULTS: Among the seven EGF-like ligands 
      examined, only amphiregulin (AREG) was expressed at higher levels in all three RA 
      tissues tested compared with the levels in OA tissues. The AREG protein 
      concentration in RA synovial fluid was also higher than that in OA synovial 
      fluid. Furthermore, recombinant human AREG stimulated FLS to proliferate and 
      produce several proinflammatory cytokines, including angiogenic cytokines such as 
      interleukin-8 and vascular endothelial growth factor (VEGF), in a dose-dependent 
      manner. The VEGF mRNA levels in RA synovia and VEGF protein concentrations in RA 
      synovial fluid were significantly higher than those in the corresponding OA 
      samples and highly correlated with the levels of AREG. CONCLUSION: The present 
      findings suggest that AREG functions to stimulate synovial cells and that 
      elevated levels of AREG may be involved in the pathogenesis of RA.
FAU - Yamane, Shoji
AU  - Yamane S
AD  - Clinical Research Center for Allergy and Rheumatology, National Hospital 
      Organization, Sagamihara National Hospital, Sakuradai 18-1, Sagamihara, Kanagawa 
      228-8522, Japan. shoji.yamane@shionogi.co.jp.
FAU - Ishida, Satoru
AU  - Ishida S
FAU - Hanamoto, Yukie
AU  - Hanamoto Y
FAU - Kumagai, Ken-Ichi
AU  - Kumagai K
FAU - Masuda, Riako
AU  - Masuda R
FAU - Tanaka, Konagi
AU  - Tanaka K
FAU - Shiobara, Noriyuki
AU  - Shiobara N
FAU - Yamane, Noriko
AU  - Yamane N
FAU - Mori, Toshihito
AU  - Mori T
FAU - Juji, Takuo
AU  - Juji T
FAU - Fukui, Naoshi
AU  - Fukui N
FAU - Itoh, Tsunetoshi
AU  - Itoh T
FAU - Ochi, Takahiro
AU  - Ochi T
FAU - Suzuki, Ryuji
AU  - Suzuki R
LA  - eng
PT  - Journal Article
DEP - 20080427
PL  - England
TA  - J Inflamm (Lond)
JT  - Journal of inflammation (London, England)
JID - 101232234
PMC - PMC2396620
EDAT- 2008/04/29 09:00
MHDA- 2008/04/29 09:01
PMCR- 2008/04/27
CRDT- 2008/04/29 09:00
PHST- 2007/10/11 00:00 [received]
PHST- 2008/04/27 00:00 [accepted]
PHST- 2008/04/29 09:00 [pubmed]
PHST- 2008/04/29 09:01 [medline]
PHST- 2008/04/29 09:00 [entrez]
PHST- 2008/04/27 00:00 [pmc-release]
AID - 1476-9255-5-5 [pii]
AID - 10.1186/1476-9255-5-5 [doi]
PST - epublish
SO  - J Inflamm (Lond). 2008 Apr 27;5:5. doi: 10.1186/1476-9255-5-5.