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

Hallbeck, Anna-Lotta (author)
Linköpings universitet,Cellbiologi,Hälsouniversitetet
Walz, Thomas M. (author)
Linköpings universitet,Onkologi,Hälsouniversitetet
Briheim, Kristina (author)
Linköpings universitet,Cellbiologi,Hälsouniversitetet
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Wasteson, Åke (author)
Linköpings universitet,Cellbiologi,Hälsouniversitetet
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 (creator_code:org_t)
2009-07-12
2005
English.
In: Scandinavian Journal of Rheumatology. - : Informa UK Limited. - 0300-9742 .- 1502-7732. ; 34:3, s. 204-211
  • Journal article (peer-reviewed)
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  • Objective: 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-) in vitro. Concomitant expression of TGF-, EGFR, and ErbB2 gives a strong proliferative drive in vitro and in vivo. However, the presence of TGF- and members of the EGFR/EGFR-ligand family has not been thoroughly investigated in joint tissue in vivo. We aimed to determine whether TGF-, EGFR, and ErbB2 are present in human synovial joints, especially during rheumatoid arthritis (RA). Methods: TGF- 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- mRNA and TGF-, ErbB2, EGFR, and CD68 immunoreactivity were detected in knee synovial biopsies (6 RA/2 OA/6 control) using in situ hybridization and immunohistochemistry. TGF- mRNA was determined in SF cells by reverse transcription polymerase chain reaction (RT-PCR) and/or the Northern blot technique. Results: TGF- protein was found in the synovial membrane (SM) and in the majority of SF samples. TGF- levels were significantly higher (p<0.001) in SF of RA patients than controls, TGF- protein and mRNA were increased and more widespread in SM of RA patients. In addition, white blood cells collected from RA SF expressed TGF- mRNA. Immunoreactivity for ErbB2 was found in SM and was more widespread in RA patients than in controls. Conclusion: The presence of TGF- in normal SF and SM may indicate a physiological maintenance function. The increased expression of TGF- and ErbB2 in RA SF and SM may give rise to an abnormal growth pattern, contributing to inflammatory synovial hyperplasia.

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