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


CONCLUSIONS
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.
Hallbeck
A L
AL
Department of Biomedicine and Surgery (IBK), Division of Cell Biology, University of Linköping, Linköping, Sweden. annha@ibk.liu.se
Walz
T M
TM
Briheim
K
K
Wasteson
A
A
D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D015870:Gene Expression; D006801:Humans; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D007962:Leukocytes / Q000378:metabolism / Q000473:pathology; D008297:Male; D020370:Osteoarthritis, Knee / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D013582:Synovial Fluid / Q000166:cytology / Q000378:metabolism; D013583:Synovial Membrane / Q000378:metabolism* / Q000473:pathology; D016211:Transforming Growth Factor alpha / Q000235:genetics / Q000378:metabolism*
D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D016211:Transforming Growth Factor alpha