TGF‐α and ErbB2 production in synovial joint tissue: increased expression in arthritic joints

Abstract

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‐α) in vitro. Concomitant expression of TGF‐α, EGFR, and ErbB2 gives a strong proliferative drive in vitro and in vivo. However, the presence of TGF‐α and members of the EGFR/EGFR‐ligand family has not been thoroughly investigated in joint tissue in vivo. We aimed to determine whether TGF‐α, EGFR, and ErbB2 are present in human synovial joints, especially during rheumatoid arthritis (RA).Methods: TGF‐α 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‐α mRNA and TGF‐α, ErbB2, EGFR, and CD68 immunoreactivity were detected in knee synovial biopsies (6 RA/2 OA/6 control) using in situ hybridization and immunohistochemistry. TGF‐α mRNA was determined in SF cells by reverse transcription polymerase chain reaction (RT‐PCR) and/or the Northern blot technique.Results: TGF‐α protein was found in the synovial membrane (SM) and in the majority of SF samples. TGF‐α levels were significantly higher (p<0.001) in SF of RA patients than controls, TGF‐α protein and mRNA were increased and more widespread in SM of RA patients. In addition, white blood cells collected from RA SF expressed TGF‐α mRNA. Immunoreactivity for ErbB2 was found in SM and was more widespread in RA patients than in controls.Conclusion: The presence of TGF‐α in normal SF and SM may indicate a physiological maintenance function. The increased expression of TGF‐α and ErbB2 in RA SF and SM may give rise to an abnormal growth pattern, contributing to inflammatory synovial hyperplasia.