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TGF-alpha and ErbB2 production in synovial joint tissue: increased expression in arthritic joints.

AbstractOBJECTIVE:
Cell types present in synovial joint tissues and during synovitis are known to produce epidermal growth factor receptor (EGFR)/ErbB-1/HER-1 and the potent EGFR-ligand transforming growth factor-alpha (TGF-alpha) in vitro. Concomitant expression of TGF-alpha, EGFR, and ErbB2 gives a strong proliferative drive in vitro and in vivo. However, the presence of TGF-alpha and members of the EGFR/EGFR-ligand family has not been thoroughly investigated in joint tissue in vivo. We aimed to determine whether TGF-alpha, EGFR, and ErbB2 are present in human synovial joints, especially during rheumatoid arthritis (RA).
METHODS:
TGF-alpha protein was immunodetected in knee synovial fluid (SF) collected from 23 RA patients, eight patients with other arthritic conditions, two osteoarthritis (OA) patients, and six post-traumatic patients (control). TGF-alpha mRNA and TGF-alpha, ErbB2, EGFR, and CD68 immunoreactivity were detected in knee synovial biopsies (6 RA/2 OA/6 control) using in situ hybridization and immunohistochemistry. TGF-alpha mRNA was determined in SF cells by reverse transcription polymerase chain reaction (RT-PCR) and/or the Northern blot technique.
RESULTS:
TGF-alpha protein was found in the synovial membrane (SM) and in the majority of SF samples. TGF-alpha levels were significantly higher (p < 0.001) in SF of RA patients than controls, TGF-alpha protein and mRNA were increased and more widespread in SM of RA patients. In addition, white blood cells collected from RA SF expressed TGF-alpha mRNA. Immunoreactivity for ErbB2 was found in SM and was more widespread in RA patients than in controls.
CONCLUSION:
The presence of TGF-alpha in normal SF and SM may indicate a physiological maintenance function. The increased expression of TGF-alpha and ErbB2 in RA SF and SM may give rise to an abnormal growth pattern, contributing to inflammatory synovial hyperplasia.
AuthorsA L Hallbeck, T M Walz, K Briheim, A Wasteson
JournalScandinavian journal of rheumatology (Scand J Rheumatol) 2005 May-Jun Vol. 34 Issue 3 Pg. 204-11 ISSN: 0300-9742 [Print] England
PMID16134726 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • RNA, Messenger
  • Transforming Growth Factor alpha
  • Receptor, ErbB-2
Topics
  • Arthritis, Rheumatoid (metabolism)
  • Female
  • Fluorescent Antibody Technique, Indirect
  • Gene Expression
  • Humans
  • Immunoenzyme Techniques
  • In Situ Hybridization
  • Leukocytes (metabolism, pathology)
  • Male
  • Osteoarthritis, Knee (metabolism)
  • RNA, Messenger (metabolism)
  • Receptor, ErbB-2 (metabolism)
  • Synovial Fluid (cytology, metabolism)
  • Synovial Membrane (metabolism, pathology)
  • Transforming Growth Factor alpha (genetics, metabolism)

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