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OBJECTIVE:Surfactant Proteins (SPs) are well known from lung and form, along with phospholipids, a surface-active-layer at the liquid-air-interface of the alveolar lining. They play a major protective role by lowering surface tension, activating innate and adaptive immune defense at the lung mucosal interface, especially during infection. We analyzed the regulation of SPs in human and mouse articular chondrocytes, synoviocytes, and synovial fluid under healthy and inflammatory conditions, as well as in tissues of patients suffering from osteoarthritis and rheumatoid arthritis. METHODS:Immunohistochemistry, RT-PCR, qRT-PCR, ELISA, Western blotting were performed in cell cultures and tissue samples to determine localization, regulation, and concentration of SPs. RESULTS:All four SPs, were expressed by healthy human and mouse articular chondrocytes and synoviocytes and were also present in synovial fluid. Treatment with inflammatory mediators like IL-1β and TNF-α led to short-term upregulation of individual SPs in vitro. In tissues from patients with osteoarthritis and rheumatoid arthritis, protein levels of all four SPs increased significantly compared to the controls used. CONCLUSION:These results show the distribution and amount of SPs in tissues of articular joints. They are produced by chondrocytes and synoviocytes and occur in measurable amounts in synovial fluid. All four SPs seem to be differently regulated under pathologic conditions. Their physiological functions in lowering surface tension and immune defense need further elucidation and make them potential candidates for therapeutic intervention.