Rheumatoid synovial cell morphologic changes induced by a mononuclear cell factor in culture

Area of Science:

• Rheumatology
• Cell Biology
• Immunology

Background:

• Adherent rheumatoid synovial cells in culture produce prostaglandin E2 (PGE2) and collagenase.
• These cells increase production of PGE2 and collagenase when exposed to a monocyte-derived factor.
• This exposure also induces a more stellate cellular morphology.

Purpose of the Study:

• To investigate the mechanisms underlying the morphologic and biochemical changes in rheumatoid synovial cells induced by a monocyte-derived factor.
• To determine the relationship between prostaglandin E2 (PGE2) production, cyclic adenosine monophosphate (cAMP) signaling, and cellular morphology.
• To elucidate the role of collagenase production in these cellular responses.

Main Methods:

• Culturing adherent rheumatoid synovial cells.
• Exposure to a monocyte-derived factor.
• Treatment with indomethacin, PGE2, 8-bromo-cAMP, colchicine, and cytochalasin B.
• Measurement of PGE2 and collagenase production.
• Observation of cellular morphology changes.

Main Results:

• A monocyte-derived factor significantly increased PGE2 and collagenase production and induced stellate morphology in synovial cells.
• Indomethacin inhibited PGE2 production and stellate changes but not collagenase production.
• PGE2 and the cAMP analog 8-bromo-cAMP reproduced the stellate morphology.
• Colchicine inhibited the morphologic transformation, while cytochalasin B had no effect.

Conclusions:

• The stellate morphology of rheumatoid synovial cells induced by the monocyte-derived factor is dependent on prostaglandin E2 (PGE2)-induced cyclic adenosine monophosphate (cAMP) stimulation.
• This morphologic change is independent of collagenase production.
• These findings suggest a specific signaling pathway involving PGE2 and cAMP in mediating cellular responses in rheumatoid synovium.